1
40
13
-
Text
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URL Address
<a href="http://doi.org/10.1161/ATVBAHA.113.301591" target="_blank" rel="noreferrer noopener">http://doi.org/10.1161/ATVBAHA.113.301591</a>
Pages
1911–1919
Issue
8
Volume
33
Dublin Core
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Title
A name given to the resource
Mitochondrial oxidative stress corrupts coronary collateral growth by activating adenosine monophosphate activated kinase-alpha signaling.
Publisher
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Arteriosclerosis, thrombosis, and vascular biology
Date
A point or period of time associated with an event in the lifecycle of the resource
2013
2013-08
Subject
The topic of the resource
AMP-Activated Protein Kinases/*metabolism; Animal; Animals; Body Weight/physiology; Cells; collateral circulation; coronary circulation; Coronary Vessels/cytology/*enzymology; Cultured; Disease Models; Endothelial Cells/cytology/*enzymology; Humans; Inbred WKY; Ischemia/metabolism/pathology; mitochondria; Mitochondria/drug effects/*metabolism; Myocardium/enzymology/pathology; Oxidative Stress/*physiology; Rats; reactive oxygen species; Rotenone/pharmacology; Signal Transduction/*physiology; TOR Serine-Threonine Kinases/metabolism; Uncoupling Agents/pharmacology
Creator
An entity primarily responsible for making the resource
Pung Yuh Fen; Sam Wai Johnn; Stevanov Kelly; Enrick Molly; Chen Chwen-Lih; Kolz Christopher; Thakker Prashanth; Hardwick James P; Chen Yeong-Renn; Dyck Jason R B; Yin Liya; Chilian William M
Description
An account of the resource
OBJECTIVE: Our goal was to determine the mechanism by which mitochondrial oxidative stress impairs collateral growth in the heart. APPROACH AND RESULTS: Rats were treated with rotenone (mitochondrial complex I inhibitor that increases reactive oxygen species production) or sham-treated with vehicle and subjected to repetitive ischemia protocol for 10 days to induce coronary collateral growth. In control rats, repetitive ischemia increased flow to the collateral-dependent zone; however, rotenone treatment prevented this increase suggesting that mitochondrial oxidative stress compromises coronary collateral growth. In addition, rotenone also attenuated mitochondrial complex I activity and led to excessive mitochondrial aggregation. To further understand the mechanistic pathway(s) involved, human coronary artery endothelial cells were treated with 50 ng/mL vascular endothelial growth factor, 1 micromol/L rotenone, and rotenone/vascular endothelial growth factor for 48 hours. Vascular endothelial growth factor induced robust tube formation; however, rotenone completely inhibited this effect (P\textless0.05 rotenone versus vascular endothelial growth factor treatment). Inhibition of tube formation by rotenone was also associated with significant increase in mitochondrial superoxide generation. Immunoblot analyses of human coronary artery endothelial cells with rotenone treatment showed significant activation of adenosine monophosphate activated kinase (AMPK)-alpha and inhibition of mammalian target of rapamycin and p70 ribosomal S6 kinase. Activation of AMPK-alpha suggested impairments in energy production, which was reflected by decrease in O2 consumption and bioenergetic reserve capacity of cultured cells. Knockdown of AMPK-alpha (siRNA) also preserved tube formation during rotenone, suggesting the negative effects were mediated by the activation of AMPK-alpha. Conversely, expression of a constitutively active AMPK-alpha blocked tube formation. CONCLUSIONS: We conclude that activation of AMPK-alpha during mitochondrial oxidative stress inhibits mammalian target of rapamycin signaling, which impairs phenotypic switching necessary for the growth of blood vessels.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1161/ATVBAHA.113.301591" target="_blank" rel="noreferrer noopener">10.1161/ATVBAHA.113.301591</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2013
AMP-Activated Protein Kinases/*metabolism
Animal
Animals
Arteriosclerosis, thrombosis, and vascular biology
Body Weight/physiology
Cells
Chen Chwen-Lih
Chen Yeong-Renn
Chilian William M
Collateral Circulation
Coronary Circulation
Coronary Vessels/cytology/*enzymology
Cultured
Department of Integrative Medical Sciences
Disease Models
Dyck Jason R B
Endothelial Cells/cytology/*enzymology
Enrick Molly
Hardwick James P
Humans
Inbred WKY
Ischemia/metabolism/pathology
Kolz Christopher
Mitochondria
Mitochondria/drug effects/*metabolism
Myocardium/enzymology/pathology
NEOMED College of Medicine
Oxidative Stress/*physiology
Pung Yuh Fen
Rats
reactive oxygen species
Rotenone/pharmacology
Sam Wai Johnn
Signal Transduction/*physiology
Stevanov Kelly
Thakker Prashanth
TOR Serine-Threonine Kinases/metabolism
Uncoupling Agents/pharmacology
Yin Liya
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1155/2009/952734" target="_blank" rel="noreferrer noopener">http://doi.org/10.1155/2009/952734</a>
Pages
952734–952734
Volume
2009
Dublin Core
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Title
A name given to the resource
PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid omega-Hydroxylase (CYP4) Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease.
Publisher
An entity responsible for making the resource available
PPAR research
Date
A point or period of time associated with an event in the lifecycle of the resource
2009
1905-07
Creator
An entity primarily responsible for making the resource
Hardwick James P; Osei-Hyiaman Douglas; Wiland Homer; Abdelmegeed Mohamed A; Song Byoung-Joon
Description
An account of the resource
Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis), due to a decrease in mitochondria beta-oxidation with an increase in both peroxisomal beta-oxidation, and microsomal omega-oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs). How steatosis increases PPARalpha activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid beta-oxidation and omega-oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) may be determined by the interplay of PPARs and HNF4alpha with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the omega-oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPARalpha. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid omega-hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA) CYP4A and long-chain fatty acid (LCFA) CYP4Fomega-hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to steatohepatitis.
Identifier
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<a href="http://doi.org/10.1155/2009/952734" target="_blank" rel="noreferrer noopener">10.1155/2009/952734</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2009
Abdelmegeed Mohamed A
Department of Integrative Medical Sciences
Hardwick James P
NEOMED College of Medicine
Osei-Hyiaman Douglas
PPAR research
Song Byoung-Joon
Wiland Homer
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1155/2009/589626" target="_blank" rel="noreferrer noopener">http://doi.org/10.1155/2009/589626</a>
Pages
589626–589626
Volume
2009
Dublin Core
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Title
A name given to the resource
PPARs, RXRs, and Drug-Metabolizing Enzymes.
Publisher
An entity responsible for making the resource available
PPAR research
Date
A point or period of time associated with an event in the lifecycle of the resource
2009
1905-07
Creator
An entity primarily responsible for making the resource
Hardwick James P; Chiang John Y L
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1155/2009/589626" target="_blank" rel="noreferrer noopener">10.1155/2009/589626</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2009
Chiang John Y L
Department of Integrative Medical Sciences
Hardwick James P
NEOMED College of Medicine
PPAR research
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1152/ajpheart.00077.2013" target="_blank" rel="noreferrer noopener">http://doi.org/10.1152/ajpheart.00077.2013</a>
Pages
H1275–1280
Issue
9
Volume
305
Dublin Core
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Title
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The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth.
Publisher
An entity responsible for making the resource available
American journal of physiology. Heart and circulatory physiology
Date
A point or period of time associated with an event in the lifecycle of the resource
2013
2013-11
Subject
The topic of the resource
*Collateral Circulation; *Coronary Circulation; *Energy Metabolism; *Neovascularization; angiogenesis; Animals; arteriogenesis; Coronary Vessels/metabolism; Humans; mitochondria; Mitochondria; Mitochondrial Proteins/metabolism; Muscle; Muscle/*metabolism; Myocytes; Oxidative Stress; Phenotype; Physiologic; Reactive Oxygen Species/*metabolism; redox-dependent signaling; Signal Transduction; Smooth; Smooth Muscle/*metabolism; Vascular/*metabolism
Creator
An entity primarily responsible for making the resource
Pung Yuh Fen; Sam Wai Johnn; Hardwick James P; Yin Liya; Ohanyan Vahagn; Logan Suzanna; Di Vincenzo Lola; Chilian William M
Description
An account of the resource
Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e., a collateral vessel, sometimes as much as an order of magnitude. An integral element of this cell proliferation is the process known as phenotypic switching in which cells of a particular phenotype, e.g., contractile vascular smooth muscle, must change their phenotype to proliferate. Phenotypic switching requires that protein synthesis occurs and different kinase signaling pathways become activated, necessitating energy to make the switch. Moreover, kinases, using ATP to phosphorylate their targets, have an energy requirement themselves. Mitochondria play a key role in the energy production that enables phenotypic switching, but under conditions where mitochondrial energy production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In addition, we discuss the potential importance of uncoupling proteins as modulators of mitochondrial reactive oxygen species production and bioenergetics, as well as the role of AMP kinase as an energy sensor upstream of mammalian target of rapamycin, the master regulator of protein synthesis.
Identifier
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<a href="http://doi.org/10.1152/ajpheart.00077.2013" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.00077.2013</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Collateral Circulation
*Coronary Circulation
*Energy Metabolism
*Neovascularization
2013
American journal of physiology. Heart and circulatory physiology
angiogenesis
Animals
Arteriogenesis
Chilian William M
Coronary Vessels/metabolism
Department of Integrative Medical Sciences
Di Vincenzo Lola
Hardwick James P
Humans
Logan Suzanna
Mitochondria
Mitochondrial Proteins/metabolism
Muscle
Muscle/*metabolism
Myocytes
NEOMED College of Medicine
Ohanyan Vahagn
Oxidative Stress
Phenotype
Physiologic
Pung Yuh Fen
Reactive Oxygen Species/*metabolism
Redox-dependent signaling
Sam Wai Johnn
Signal Transduction
Smooth
Smooth Muscle/*metabolism
Vascular/*metabolism
Yin Liya
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/S1054-3589(15)00047-2" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/S1054-3589(15)00047-2</a>
Pages
xv–xxxi
Volume
74
Dublin Core
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Title
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Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer. Preface.
Publisher
An entity responsible for making the resource available
Advances in pharmacology (San Diego, Calif.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2015
1905-7
Subject
The topic of the resource
Animals; Cytochrome P-450 Enzyme System/*metabolism; Humans; Inflammation/*metabolism; Neoplasms/*metabolism
Creator
An entity primarily responsible for making the resource
Hardwick James P
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/S1054-3589(15)00047-2" target="_blank" rel="noreferrer noopener">10.1016/S1054-3589(15)00047-2</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2015
Advances in pharmacology (San Diego, Calif.)
Animals
Cytochrome P-450 Enzyme System/*metabolism
Department of Integrative Medical Sciences
Hardwick James P
Humans
Inflammation/*metabolism
NEOMED College of Medicine
Neoplasms/*metabolism
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bcp.2008.03.004" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bcp.2008.03.004</a>
Pages
2263–2275
Issue
12
Volume
75
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Cytochrome P450 omega hydroxylase (CYP4) function in fatty acid metabolism and metabolic diseases.
Publisher
An entity responsible for making the resource available
Biochemical pharmacology
Date
A point or period of time associated with an event in the lifecycle of the resource
2008
2008-06
Subject
The topic of the resource
*Cytochrome P-450 Enzyme System/genetics/metabolism/physiology; Animals; Cytochrome P-450 CYP4A/genetics/metabolism/physiology; Enzymologic; Fatty Acids/*metabolism; Gene Expression Regulation; Humans; Metabolic Diseases/enzymology/*metabolism
Creator
An entity primarily responsible for making the resource
Hardwick James P
Description
An account of the resource
The cytochrome P450 gene 4 family (CYP4) consists of a group of over 63 members that omega-hydroxylate the terminal carbon of fatty acids. In mammals, six subfamilies have been identified and three of these subfamily members show a preference in the metabolism of short (C7-C10)-CYP4B, medium (C10-C16)-CYP4A, and long (C16-C26)-CYP4F, saturated, unsaturated and branched chain fatty acids. These omega-hydroxylated fatty acids are converted to dicarboxylic acids, which are preferentially metabolized by the peroxisome beta-oxidation system to shorter chain fatty acids that are transported to the mitochondria for complete oxidation or used either to supply energy for peripheral tissues during starvation or in lipid synthesis. The differential regulation of the CYP4A and CYP4F genes during fasting, by peroxisome proliferators and in non-alcoholic fatty liver disease (NAFLD) suggests different roles in lipid metabolism. The omega-hydroxylation and inactivation of pro-inflammatory eicosanoids by members of the CYP4F subfamily and the association of the CYP4F2 and CYP4F3 genes with inflammatory celiac disease indicate an important role in the resolution of inflammation. Several human diseases have been genetically linked to the expression CYP4 gene polymorphic variants, which may link human susceptibility to diseases of lipid metabolism and the activation and resolution phases of inflammation. Understanding how the CYP4 genes are regulated during the fasting and feeding cycles and by endogenous lipids will provide therapeutic avenues in the treatment of metabolic disorders of lipid metabolism and inflammation.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bcp.2008.03.004" target="_blank" rel="noreferrer noopener">10.1016/j.bcp.2008.03.004</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Cytochrome P-450 Enzyme System/genetics/metabolism/physiology
2008
Animals
Biochemical pharmacology
Cytochrome P-450 CYP4A/genetics/metabolism/physiology
Department of Integrative Medical Sciences
Enzymologic
Fatty Acids/*metabolism
Gene Expression Regulation
Hardwick James P
Humans
Metabolic Diseases/enzymology/*metabolism
NEOMED College of Medicine
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.abb.2008.01.018" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.abb.2008.01.018</a>
Pages
1–16
Issue
1
Volume
472
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Genomic structure and regulation of the rat hepatic CYP4F1 gene by peroxisome proliferators.
Publisher
An entity responsible for making the resource available
Archives of biochemistry and biophysics
Date
A point or period of time associated with an event in the lifecycle of the resource
2008
2008-04
Subject
The topic of the resource
Animals; Cell Line; Chromosome Mapping; Cytochrome P-450 Enzyme System/*genetics; Gene Expression Regulation/drug effects/*genetics; Genetic/*genetics; Hepatocytes/drug effects/*physiology; Liver/drug effects/*physiology; Peroxisome Proliferator-Activated Receptors/*genetics; Peroxisome Proliferators/*pharmacology; Promoter Regions; Rats
Creator
An entity primarily responsible for making the resource
Donelson Ellen; Chen Liping; Zhang Xiaolan; Goswami Puja; Song Byoung J; Hardwick James P
Description
An account of the resource
The rat hepatic gene CYP4F1 encodes a fatty acid omega hydroxylase P450 that metabolizes proinflammatory eicosanoids and long-chain fatty acids. We have completely sequenced the CYP4F1 gene (Accession Nos. AF200361 and AF181083), identified multiple transcription start sites, and characterized a strong core promoter region, -760/116, induced by retinoic acids and peroxisome proliferators in rat hepatoma McA-RH7777 cells. Three peroxisome proliferator responsive elements (PPRE) bind both PPARalpha/RXRalpha and HNF4alpha. Co-transfection of McA-RH7777 cells with the -760/116 reporter construct and PPARalpha/RXRalpha or HNF4alpha showed that HNF4alpha activated while PPARalpha/RXRalpha inhibited CYP4F1 promoter activity. Treating cells with Wy14,643 reversed all initial effects, indicating co-regulation of CYP4F1 gene transcription by PPARalpha/RXRalpha and HNF4alpha. Chromatin immunoprecipitation analysis of cells treated with Wy14,643 showed association of PPARalpha/RXRalpha with the active transcription of the CYP4F1 gene while in clofibrate treated rats HNF4alpha binds during gene repression, suggesting differential regulation of the CYP4F1 gene in vivo and in cell lines.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.abb.2008.01.018" target="_blank" rel="noreferrer noopener">10.1016/j.abb.2008.01.018</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2008
Animals
Archives of biochemistry and biophysics
Cell Line
Chen Liping
Chromosome Mapping
Cytochrome P-450 Enzyme System/*genetics
Department of Integrative Medical Sciences
Donelson Ellen
Gene Expression Regulation/drug effects/*genetics
Genetic/*genetics
Goswami Puja
Hardwick James P
Hepatocytes/drug effects/*physiology
Liver/drug effects/*physiology
NEOMED College of Medicine
Peroxisome Proliferator-Activated Receptors/*genetics
Peroxisome Proliferators/*pharmacology
Promoter Regions
Rats
Song Byoung J
Zhang Xiaolan
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/bs.apha.2015.04.002" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/bs.apha.2015.04.002</a>
Pages
303–372
Volume
74
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease.
Publisher
An entity responsible for making the resource available
Advances in pharmacology (San Diego, Calif.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2015
2015
Subject
The topic of the resource
Alcohol-metabolizing enzymes; Alcoholic/*enzymology/*metabolism; ALDH2; Animals; CYP2E1; Cytochrome P-450 CYP2E1/*metabolism; Ethanol/*metabolism; Humans; Liver disease; Liver Diseases; Mitochondrial dysfunction; Nitroxidative stress; Non-alcoholic Fatty Liver Disease/*enzymology/*metabolism; Posttranslational modifications
Creator
An entity primarily responsible for making the resource
Song Byoung-Joon; Akbar Mohammed; Jo Inho; Hardwick James P; Abdelmegeed Mohamed A
Description
An account of the resource
Fat accumulation (hepatic steatosis) in alcoholic and nonalcoholic fatty liver disease is a potentially pathologic condition which can progress to steatohepatitis (inflammation), fibrosis, cirrhosis, and carcinogenesis. Many clinically used drugs or some alternative medicine compounds are also known to cause drug-induced liver injury, which can further lead to fulminant liver failure and acute deaths in extreme cases. During liver disease process, certain cytochromes P450 such as the ethanol-inducible cytochrome P450-2E1 (CYP2E1) and CYP4A isozymes can be induced and/or activated by alcohol and/or high-fat diets and pathophysiological conditions such as fasting, obesity, and diabetes. Activation of these P450 isozymes, involved in the metabolism of ethanol, fatty acids, and various drugs, can produce reactive oxygen/nitrogen species directly and/or indirectly, contributing to oxidative modifications of DNA/RNA, proteins and lipids. In addition, aldehyde dehydrogenases including the mitochondrial low Km aldehyde dehydrogenase-2 (ALDH2), responsible for the metabolism of acetaldehyde and lipid aldehydes, can be inactivated by various hepatotoxic agents. These highly reactive acetaldehyde and lipid peroxides, accumulated due to ALDH2 suppression, can interact with cellular macromolecules DNA/RNA, lipids, and proteins, leading to suppression of their normal function, contributing to DNA mutations, endoplasmic reticulum stress, mitochondrial dysfunction, steatosis, and cell death. In this chapter, we specifically review the roles of the alcohol-metabolizing enzymes including the alcohol dehydrogenase, ALDH2, CYP2E1, and other enzymes in promoting liver disease. We also discuss translational research opportunities with natural and/or synthetic antioxidants, which can prevent or delay the onset of inflammation and liver disease.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/bs.apha.2015.04.002" target="_blank" rel="noreferrer noopener">10.1016/bs.apha.2015.04.002</a>
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Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2015
Abdelmegeed Mohamed A
Advances in pharmacology (San Diego, Calif.)
Akbar Mohammed
Alcohol-metabolizing enzymes
Alcoholic/*enzymology/*metabolism
ALDH2
Animals
CYP2E1
Cytochrome P-450 CYP2E1/*metabolism
Department of Integrative Medical Sciences
Ethanol/*metabolism
Hardwick James P
Humans
Jo Inho
Liver disease
Liver Diseases
Mitochondrial dysfunction
NEOMED College of Medicine
Nitroxidative stress
Non-alcoholic Fatty Liver Disease/*enzymology/*metabolism
Posttranslational modifications
Song Byoung-Joon
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/B978-0-12-404717-4.00005-6" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/B978-0-12-404717-4.00005-6</a>
Pages
157–266
Volume
66
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Eicosanoids in metabolic syndrome.
Publisher
An entity responsible for making the resource available
Advances in pharmacology (San Diego, Calif.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2013
1905-7
Subject
The topic of the resource
Adipose Tissue; Animals; Eicosanoids/*metabolism; Fatty Liver/etiology/immunology/metabolism; Humans; Immune System/immunology/metabolism; Lipid Metabolism; Metabolic Syndrome/complications/immunology/*metabolism/physiopathology; Non-alcoholic Fatty Liver Disease; Obesity/complications/immunology/metabolism; Sepsis/complications/immunology/metabolism; White/immunology/metabolism
Creator
An entity primarily responsible for making the resource
Hardwick James P; Eckman Katie; Lee Yoon-Kwang; Abdelmegeed Mohamed A; Esterle Andrew; Chilian William M; Chiang John Y; Song Byoung-Joon
Description
An account of the resource
Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism. The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS.
Identifier
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<a href="http://doi.org/10.1016/B978-0-12-404717-4.00005-6" target="_blank" rel="noreferrer noopener">10.1016/B978-0-12-404717-4.00005-6</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2013
Abdelmegeed Mohamed A
Adipose Tissue
Advances in pharmacology (San Diego, Calif.)
Animals
Chiang John Y
Chilian William M
Department of Integrative Medical Sciences
Eckman Katie
Eicosanoids/*metabolism
Esterle Andrew
Fatty Liver/etiology/immunology/metabolism
Hardwick James P
Humans
Immune System/immunology/metabolism
Lee Yoon-Kwang
Lipid Metabolism
Metabolic Syndrome/complications/immunology/*metabolism/physiopathology
NEOMED College of Medicine
Non-alcoholic Fatty Liver Disease
Obesity/complications/immunology/metabolism
Sepsis/complications/immunology/metabolism
Song Byoung-Joon
White/immunology/metabolism
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1007/s00395-016-0547-4" target="_blank" rel="noreferrer noopener">http://doi.org/10.1007/s00395-016-0547-4</a>
Pages
29–29
Issue
3
Volume
111
Dublin Core
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Title
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Impaired coronary metabolic dilation in the metabolic syndrome is linked to mitochondrial dysfunction and mitochondrial DNA damage.
Publisher
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Basic research in cardiology
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-05
Subject
The topic of the resource
Animal; Animals; Coronary circulation; Coronary microcirculation; Coronary Vessels/metabolism/*physiopathology; Diabetes; Disease Models; DNA; DNA Damage/physiology; DNA Fragmentation; Metabolic Syndrome/metabolism/*physiopathology; Mitochondria; Mitochondria/*metabolism; Mitochondrial/*metabolism; Obesity; Oxidative Stress/physiology; Rats; Reactive Oxygen Species/metabolism; Vasodilation/physiology; Zucker
Creator
An entity primarily responsible for making the resource
Guarini Giacinta; Kiyooka Takahiko; Ohanyan Vahagn; Pung Yuh Fen; Marzilli Mario; Chen Yeong-Renn; Chen Chwen-Lih; Kang Patrick T; Hardwick James P; Kolz Christopher L; Yin Liya; Wilson Glenn L; Shokolenko Inna; Dobson James G Jr; Fenton Richard; Chilian William M
Description
An account of the resource
Mitochondrial dysfunction in obesity and diabetes can be caused by excessive production of free radicals, which can damage mitochondrial DNA. Because mitochondrial DNA plays a key role in the production of ATP necessary for cardiac work, we hypothesized that mitochondrial dysfunction, induced by mitochondrial DNA damage, uncouples coronary blood flow from cardiac work. Myocardial blood flow (contrast echocardiography) was measured in Zucker lean (ZLN) and obese fatty (ZOF) rats during increased cardiac metabolism (product of heart rate and arterial pressure, i.v. norepinephrine). In ZLN increased metabolism augmented coronary blood flow, but in ZOF metabolic hyperemia was attenuated. Mitochondrial respiration was impaired and ROS production was greater in ZOF than ZLN. These were associated with mitochondrial DNA (mtDNA) damage in ZOF. To determine if coronary metabolic dilation, the hyperemic response induced by heightened cardiac metabolism, is linked to mitochondrial function we introduced recombinant proteins (intravenously or intraperitoneally) in ZLN and ZOF to fragment or repair mtDNA, respectively. Repair of mtDNA damage restored mitochondrial function and metabolic dilation, and reduced ROS production in ZOF; whereas induction of mtDNA damage in ZLN reduced mitochondrial function, increased ROS production, and attenuated metabolic dilation. Adequate metabolic dilation was also associated with the extracellular release of ADP, ATP, and H2O2 by cardiac myocytes; whereas myocytes from rats with impaired dilation released only H2O2. In conclusion, our results suggest that mitochondrial function plays a seminal role in connecting myocardial blood flow to metabolism, and integrity of mtDNA is central to this process.
Identifier
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<a href="http://doi.org/10.1007/s00395-016-0547-4" target="_blank" rel="noreferrer noopener">10.1007/s00395-016-0547-4</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2016
Animal
Animals
Basic research in cardiology
Chen Chwen-Lih
Chen Yeong-Renn
Chilian William M
Coronary Circulation
Coronary microcirculation
Coronary Vessels/metabolism/*physiopathology
Department of Integrative Medical Sciences
Diabetes
Disease Models
DNA
DNA Damage/physiology
DNA Fragmentation
Dobson James G Jr
Fenton Richard
Guarini Giacinta
Hardwick James P
Kang Patrick T
Kiyooka Takahiko
Kolz Christopher L
Marzilli Mario
Metabolic Syndrome/metabolism/*physiopathology
Mitochondria
Mitochondria/*metabolism
Mitochondrial/*metabolism
NEOMED College of Medicine
Obesity
Ohanyan Vahagn
Oxidative Stress/physiology
Pung Yuh Fen
Rats
Reactive Oxygen Species/metabolism
Shokolenko Inna
Vasodilation/physiology
Wilson Glenn L
Yin Liya
Zucker
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1002/hep4.1120" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep4.1120</a>
Pages
1085–1098
Issue
10
Volume
1
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Hairy and enhancer of split 6 prevents hepatic lipid accumulation through inhibition of Pparg2 expression.
Publisher
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Hepatology communications
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-12
Creator
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Park Jung Eun; Lee Mikang; Kim Seong-Chul; Zhang Yanqiao; Hardwick James P; Lee Yoon-Kwang
Description
An account of the resource
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a master regulator for white adipocyte differentiation and lipid storage. The increased level of hepatic PPARgamma2 isoform reprograms liver for lipid storage and causes abnormal fat accumulation in certain pathophysiologic conditions. The current study aimed to investigate a role of transcriptional repressor hairy and enhancer of split 6 (HES6) in the regulation of Pparg2 expression and hepatic steatosis induced by diet. Liver-specific overexpression of Hes6 using adenovirus reduced Pparg2 messenger RNA levels by 90% and hepatic triglyceride accumulation by 22% compared to the levels in mice injected with an adenoviral empty vector with Western diet feeding. In sharp contrast, silencing Hes6 gene expression using short hairpin RNA increased hepatic lipid accumulation and Pparg2 messenger RNA levels by 70% and 4-fold, respectively. To locate hepatocyte nuclear factor 4 alpha (HNF4alpha) binding site(s), through which repressional activity of HES6 is mediated, a 2.5-kb Pparg2 promoter-driven luciferase reporter was constructed for transient transfection assays. Subsequently, chromatin immunoprecipitation and electrophoretic mobility shift assays were performed. An HNF4alpha binding consensus sequence was identified at 903 base pairs upstream from the transcription start site of Pparg2. Deletion or point mutation of the sequence in a luciferase reporter containing the Pparg2 promoter abolished HNF4alpha-mediated activation in HeLa cells. Chromatin immunoprecipitation and electrophoretic mobility shift assays further confirmed direct recruitment and binding of HNF4alpha to the site. Gene expression analysis with liver samples from subjects with nonalcoholic steatohepatitis suggested that the axis of the Hes6-Hnf4a-Pparg2 transcriptional cascade is also responsible for hepatic fat accumulation in humans. Conclusion: HES6 represses Pparg2 gene expression, thereby preventing hepatic lipid accumulation induced by chronic Western diet feeding or pathophysiologic conditions. (Hepatology Communications 2017;1:1085-1098).
Identifier
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<a href="http://doi.org/10.1002/hep4.1120" target="_blank" rel="noreferrer noopener">10.1002/hep4.1120</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2017
Department of Integrative Medical Sciences
Hardwick James P
Hepatology communications
Kim Seong-Chul
Lee Mikang
Lee Yoon-Kwang
NEOMED College of Medicine
Park Jung Eun
Zhang Yanqiao
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1002/hep4.1066" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep4.1066</a>
Pages
675–690
Issue
7
Volume
1
Dublin Core
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Title
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Increased ethanol-inducible cytochrome P450-2E1 and cytochrome P450 isoforms in exosomes of alcohol-exposed rodents and patients with alcoholism through oxidative and endoplasmic reticulum stress.
Publisher
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Hepatology communications
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-09
Creator
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Cho Young-Eun; Mezey Esteban; Hardwick James P; Salem Norman Jr; Clemens Dahn L; Song Byoung-Joon
Description
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This study investigated the role of ethanol-inducible cytochrome P450-2E1 (CYP2E1) in enhancing CYP2E1 and other P450 proteins in extracellular vesicles (EVs) from alcohol-exposed rodents and human patients with alcoholism and their effects on oxidative hepatocyte injury. Female Fischer rats and wild-type or Cyp2e1-null mice were exposed to three oral doses of binge ethanol or dextrose control at 12-hour intervals. Plasma EV and hepatic proteins from alcohol-exposed rodents, patients with alcoholism, and their respective controls were isolated and characterized. The number of EVs and the amounts of EV CYP2E1, CYP2A, CYP1A1/2, and CYP4B proteins were markedly elevated in both patients with alcoholism and alcohol-exposed rats and mice. The number of EVs and EV P450 proteins were significantly reduced in ethanol-exposed rats fed a diet containing polyunsaturated fatty acids. The increased number of EVs and EV CYP2E1 and other P450 isoforms in alcohol-exposed wild types were significantly reduced in the corresponding Cyp2e1-null mice. EV CYP2E1 amounts depended on increased oxidative and endoplasmic reticulum (ER) stress because their levels were decreased by cotreatment with the antioxidant N-acetylcysteine or the CYP2E1 inhibitor chlormethiazole but increased by ER stress-inducer thapsigargin, which was blocked by 4-phenylbutyric acid. Furthermore, cell death rates were elevated when primary hepatocytes or human hepatoma cells were exposed to EVs from alcohol-exposed rodents and patients with alcoholism, demonstrating that EVs from alcohol-exposed rats and patients with alcoholism are functional and can promote cell death by activating the apoptosis signaling pathway, including phospho-c-Jun
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/hep4.1066" target="_blank" rel="noreferrer noopener">10.1002/hep4.1066</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2017
Cho Young-Eun
Clemens Dahn L
Department of Integrative Medical Sciences
Hardwick James P
Hepatology communications
Mezey Esteban
NEOMED College of Medicine
Salem Norman Jr
Song Byoung-Joon
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1002/hep.26699" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.26699</a>
Pages
1750–1760
Issue
5
Volume
59
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
All-trans-retinoic acid ameliorates hepatic steatosis in mice by a novel transcriptional cascade.
Publisher
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Hepatology (Baltimore, Md.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-05
Subject
The topic of the resource
Animals; Basic Helix-Loop-Helix Transcription Factors/genetics; Blood Glucose/analysis; Cytoplasmic and Nuclear/*physiology; Fatty Liver/*drug therapy/metabolism; Gene Expression Regulation; Genetic; Inbred C57BL; Lipid Metabolism; Liver/metabolism; Male; Mice; Non-alcoholic Fatty Liver Disease; PPAR gamma/*genetics; Receptors; Repressor Proteins/genetics; Retinoic Acid Receptor alpha; Retinoic Acid/physiology; Transcription; Tretinoin/pharmacology/*therapeutic use
Creator
An entity primarily responsible for making the resource
Kim Seong-Chul; Kim Chun-Ki; Axe David; Cook Aaron; Lee Mikang; Li Tiangang; Smallwood Nicole; Chiang John Y L; Hardwick James P; Moore David D; Lee Yoon-Kwang
Description
An account of the resource
UNLABELLED: Mice deficient in small heterodimer partner (SHP) are protected from diet-induced hepatic steatosis resulting from increased fatty acid oxidation and decreased lipogenesis. The decreased lipogenesis appears to be a direct consequence of very low expression of peroxisome proliferator-activated receptor gamma 2 (PPAR-gamma2), a potent lipogenic transcription factor, in the SHP(-/-) liver. The current study focused on the identification of a SHP-dependent regulatory cascade that controls PPAR-gamma2 gene expression, thereby regulating hepatic fat accumulation. Illumina BeadChip array (Illumina, Inc., San Diego, CA) and real-time polymerase chain reaction were used to identify genes responsible for the linkage between SHP and PPAR-gamma2 using hepatic RNAs isolated from SHP(-/-) and SHP-overexpressing mice. The initial efforts identify that hairy and enhancer of split 6 (Hes6), a novel transcriptional repressor, is an important mediator of the regulation of PPAR-gamma2 transcription by SHP. The Hes6 promoter is specifically activated by the retinoic acid receptor (RAR) in response to its natural agonist ligand, all-trans retinoic acid (atRA), and is repressed by SHP. Hes6 subsequently represses hepatocyte nuclear factor 4 alpha (HNF-4alpha)-activated PPAR-gamma2 gene expression by direct inhibition of
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/hep.26699" target="_blank" rel="noreferrer noopener">10.1002/hep.26699</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2014
Animals
Axe David
Basic Helix-Loop-Helix Transcription Factors/genetics
Blood Glucose/analysis
Chiang John Y L
Cook Aaron
Cytoplasmic and Nuclear/*physiology
Department of Integrative Medical Sciences
Department of Pharmaceutical Sciences
Fatty Liver/*drug therapy/metabolism
Gene Expression Regulation
Genetic
Hardwick James P
Hepatology (Baltimore, Md.)
Inbred C57BL
Kim Chun-Ki
Kim Seong-Chul
Lee Mikang
Lee Yoon-Kwang
Li Tiangang
Lipid Metabolism
Liver/metabolism
Male
Mice
Moore David D
NEOMED College of Medicine
NEOMED College of Pharmacy
Non-alcoholic Fatty Liver Disease
PPAR gamma/*genetics
Receptors
Repressor Proteins/genetics
Retinoic Acid Receptor alpha
Retinoic Acid/physiology
Smallwood Nicole
Transcription
Tretinoin/pharmacology/*therapeutic use