1
40
9
-
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/ardp.201500293" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/ardp.201500293</a>
Pages
252–267
Issue
4
Volume
349
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
Synthesis and Biological Evaluation of Pentacycloundecylamines and Triquinylamines as Voltage-Gated Calcium Channel Blockers.
Publisher
An entity responsible for making the resource available
Archiv der Pharmazie
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-04
Subject
The topic of the resource
Alicyclic/chemical synthesis/*chemistry/pharmacology; Amines/chemical synthesis/*chemistry/pharmacology; Animals; Apoptosis/drug effects; Calcium Channel Blockers/chemical synthesis/*chemistry/pharmacology; Calcium Channels; Calcium/*metabolism; Cell Survival/drug effects; Hydrocarbons; Hydrogen Peroxide/pharmacology; L-Lactate Dehydrogenase/metabolism; L-type calcium channel (LTCC) blockers; L-Type/*metabolism; Multifunctional drugs; Neurodegeneration; PC12 Cells; Pentacycloundecylamine; Quinones/chemical synthesis/*chemistry/pharmacology; Rats; Structure-Activity Relationship; Triquinylamine
Creator
An entity primarily responsible for making the resource
Young Lois-May; Geldenhuys Werner J; Domingo Olwen C; Malan Sarel F; Van der Schyf Cornelis J
Description
An account of the resource
Preclinical studies for neurodegenerative diseases have shown a multi-targeted approach to be successful in the treatment of these complex disorders with several pathoetiological pathways. Polycyclic compounds, such as NGP1-01 (7a), have demonstrated the ability to target multiple mechanisms of the complex etiology and are referred to as multifunctional compounds. These compounds have served as scaffolds with the ability to attenuate Ca(2+) overload and excitotoxicity through several pathways. In this study, our focus was on mitigating Ca(2+) overload through the L-type calcium channels (LTCC). Here, we report the synthesis and biological evaluation of several novel polycyclic compounds. We determined the IC50 values for both the pentacycloundecylamines and the triquinylamines by means of a high-throughput fluorescence calcium flux assay utilizing Fura-2/AM. The potential of these compounds to offer protection against hydrogen peroxide-induced cell death was also evaluated. Overall,
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/ardp.201500293" target="_blank" rel="noreferrer noopener">10.1002/ardp.201500293</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
Alicyclic/chemical synthesis/*chemistry/pharmacology
Amines/chemical synthesis/*chemistry/pharmacology
Animals
Apoptosis/drug effects
Archiv der Pharmazie
Calcium Channel Blockers/chemical synthesis/*chemistry/pharmacology
Calcium Channels
Calcium/*metabolism
Cell Survival/drug effects
Domingo Olwen C
Geldenhuys Werner J
Hydrocarbons
Hydrogen Peroxide/pharmacology
L-Lactate Dehydrogenase/metabolism
L-type calcium channel (LTCC) blockers
L-Type/*metabolism
Malan Sarel F
Multifunctional drugs
Neurodegeneration
PC12 Cells
Pentacycloundecylamine
Quinones/chemical synthesis/*chemistry/pharmacology
Rats
Structure-Activity Relationship
Triquinylamine
Van der Schyf Cornelis J
Young Lois-May
-
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/jnr.490350207" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/jnr.490350207</a>
Pages
170–182
Issue
2
Volume
35
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
Serotonin-activated alpha 2-macroglobulin inhibits neurite outgrowth and survival of embryonic sensory and cerebral cortical neurons.
Publisher
An entity responsible for making the resource available
Journal of neuroscience research
Date
A point or period of time associated with an event in the lifecycle of the resource
1993
1993-06
Subject
The topic of the resource
Afferent/drug effects/ultrastructure; alpha-Macroglobulins/metabolism/*pharmacology; Animals; Bovine/pharmacology; Cell Survival/drug effects; Cells; Chick Embryo; Cultured; Frontal Lobe/*cytology/embryology; Ganglia; Humans; Nerve Growth Factors/*antagonists & inhibitors/pharmacology; Neurites/drug effects/ultrastructure; Neurons; Neurons/*drug effects/ultrastructure; Protein Binding; Rats; Serotonin/metabolism/*pharmacology; Serum Albumin; Spinal/*cytology/embryology
Creator
An entity primarily responsible for making the resource
Liebl D J; Koo P H
Description
An account of the resource
Methylamine-modified alpha-2-macroglobulin (MA-alpha 2M) has been recently shown to inhibit the biological activity of beta-nerve growth factor (NGF) in promoting neurite outgrowth by embryonic dorsal root ganglia in culture (Koo PH, Liebl DJ, J Neurosci Res 31:678-692, 1992). The objectives of this study are to determine whether alpha 2M can also be modified by larger aromatic biogenic amines such as
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/jnr.490350207" target="_blank" rel="noreferrer noopener">10.1002/jnr.490350207</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).
1993
Afferent/drug effects/ultrastructure
alpha-Macroglobulins/metabolism/*pharmacology
Animals
Bovine/pharmacology
Cell Survival/drug effects
Cells
Chick Embryo
Cultured
Frontal Lobe/*cytology/embryology
Ganglia
Humans
Journal of neuroscience research
Koo P H
Liebl D J
Nerve Growth Factors/*antagonists & inhibitors/pharmacology
Neurites/drug effects/ultrastructure
Neurons
Neurons/*drug effects/ultrastructure
Protein Binding
Rats
Serotonin/metabolism/*pharmacology
Serum Albumin
Spinal/*cytology/embryology
-
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.bmcl.2014.07.072" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2014.07.072</a>
Pages
4553–4556
Issue
18
Volume
24
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
Screening and identification of novel compounds with potential anti-proliferative effects on gallium-resistant lung cancer through an AXL kinase pathway.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-09
Subject
The topic of the resource
Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology; Antitumor; AXL; Cell Line; Cell Proliferation/drug effects; Cell Survival/drug effects; Dose-Response Relationship; Drug; Drug Resistance; Drug Screening Assays; Gallium; Gallium-resistance; Gallium/pharmacology; Humans; Lung cancer; Lung Neoplasms/drug therapy/*enzymology/*pathology; Molecular Structure; Naphthalenes/chemistry/*pharmacology; Neoplasm/drug effects; Proto-Oncogene Proteins/*antagonists & inhibitors/metabolism; Pyrazoles/chemistry/*pharmacology; Quinolines/chemistry/*pharmacology; Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism; Structure-Activity Relationship; Tetrazoles/chemistry/*pharmacology; Tumor; Virtual screening
Creator
An entity primarily responsible for making the resource
Oyewumi Moses O; Alazizi Adnan; Liva Sophia; Lin Li; Geldenhuys Werner J
Description
An account of the resource
The clinical application of gallium compounds as anticancer agents is hampered by development of resistance. As a potential strategy to overcome the limitation, eight series of compounds were identified through virtual screening of AXL kinase homology model. Anti-proliferative studies were carried using gallium-sensitive (S) and gallium-resistant (R) human lung adenocarcinoma (A549) cells. Compounds 5476423 and 7919469 were identified as leads. The IC50 values from treating
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2014.07.072" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2014.07.072</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).
2014
Alazizi Adnan
Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology
Antitumor
AXL
Bioorganic & medicinal chemistry letters
Cell Line
Cell Proliferation/drug effects
Cell Survival/drug effects
Department of Pharmaceutical Sciences
Dose-Response Relationship
Drug
Drug Resistance
Drug Screening Assays
Gallium
Gallium-resistance
Gallium/pharmacology
Geldenhuys Werner J
Humans
Lin Li
Liva Sophia
Lung cancer
Lung Neoplasms/drug therapy/*enzymology/*pathology
Molecular Structure
Naphthalenes/chemistry/*pharmacology
NEOMED College of Pharmacy
Neoplasm/drug effects
Oyewumi Moses O
Proto-Oncogene Proteins/*antagonists & inhibitors/metabolism
Pyrazoles/chemistry/*pharmacology
Quinolines/chemistry/*pharmacology
Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism
Structure-Activity Relationship
Tetrazoles/chemistry/*pharmacology
Tumor
Virtual screening
-
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.freeradbiomed.2011.05.034" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.freeradbiomed.2011.05.034</a>
Pages
876–883
Issue
4
Volume
51
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
Vitamin B12 protects against superoxide-induced cell injury in human aortic endothelial cells.
Publisher
An entity responsible for making the resource available
Free radical biology & medicine
Date
A point or period of time associated with an event in the lifecycle of the resource
2011
2011-08
Subject
The topic of the resource
Aorta/pathology; Apoptosis/drug effects; Atherosclerosis/*drug therapy/metabolism/pathology/physiopathology; Cell Line; Cell Survival/drug effects; Cytoprotection; Endothelium; Free Radical Scavengers/*pharmacology; Humans; Mitochondria/drug effects/metabolism/pathology; Oxidative Stress/drug effects; Reperfusion Injury/*drug therapy/metabolism/pathology/physiopathology; Superoxides/metabolism; Vascular/*drug effects/metabolism/pathology; Vitamin B 12/*pharmacology; Vitamin B Complex/*pharmacology
Creator
An entity primarily responsible for making the resource
Moreira Edward S; Brasch Nicola E; Yun June
Description
An account of the resource
Superoxide (O(2)(*-)) is implicated in inflammatory states including arteriosclerosis and ischemia-reperfusion injury. Cobalamin (Cbl) supplementation is beneficial for treating many inflammatory diseases and also provides protection in oxidative-stress-associated pathologies. Reduced Cbl reacts with O(2)(*-) at rates approaching that of superoxide dismutase (SOD), suggesting a plausible mechanism for its anti-inflammatory properties. Elevated homocysteine (Hcy) is an independent risk factor for cardiovascular disease and endothelial dysfunction. Hcy increases O(2)(*-) levels in human aortic endothelial cells (HAEC). Here, we explore the protective effects of Cbl in HAEC exposed to various O(2)(*-) sources, including increased Hcy levels. Hcy increased O(2)(*-) levels (1.6-fold) in HAEC, concomitant with a 20% reduction in cell viability and a 1.5-fold increase in apoptotic death. Pretreatment of HAEC with physiologically relevant concentrations of cyanocobalamin (CNCbl) (10-50nM) prevented Hcy-induced increases in O(2)(*-) and cell death. CNCbl inhibited both Hcy and rotenone-induced mitochondrial O(2)(*-) production. Similarly, HAEC challenged with paraquat showed a 1.5-fold increase in O(2)(*-) levels and a 30% decrease in cell viability, both of which were prevented with CNCbl pretreatment. CNCbl also attenuated elevated O(2)(*-) levels after exposure of cells to a Cu/Zn-SOD inhibitor. Our data suggest that Cbl acts as an efficient intracellular O(2)(*-) scavenger.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.freeradbiomed.2011.05.034" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2011.05.034</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).
2011
Aorta/pathology
Apoptosis/drug effects
Atherosclerosis/*drug therapy/metabolism/pathology/physiopathology
Brasch Nicola E
Cell Line
Cell Survival/drug effects
Cytoprotection
Department of Integrative Medical Sciences
Endothelium
Free radical biology & medicine
Free Radical Scavengers/*pharmacology
Humans
Mitochondria/drug effects/metabolism/pathology
Moreira Edward S
NEOMED College of Medicine
Oxidative Stress/drug effects
Reperfusion Injury/*drug therapy/metabolism/pathology/physiopathology
Superoxides/metabolism
Vascular/*drug effects/metabolism/pathology
Vitamin B 12/*pharmacology
Vitamin B Complex/*pharmacology
Yun June
-
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.neuropharm.2017.07.020" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.neuropharm.2017.07.020</a>
Pages
189–196
Volume
125
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
Valproate increases dopamine transporter expression through histone acetylation and enhanced promoter binding of Nurr1.
Publisher
An entity responsible for making the resource available
Neuropharmacology
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-10
Subject
The topic of the resource
Acetylation/drug effects; Animals; Butyrates/pharmacology; Cell Line; Cell Survival/drug effects; Dopamine Plasma Membrane Transport Proteins/*metabolism; Dopamine transporter; Dopaminergic Neurons/cytology/drug effects/metabolism; Dose-Response Relationship; Drug; Epigenesis; Epigenetics; Genetic; Genetic/drug effects; Group A; HDAC; Histone deacetylase; Histone Deacetylase Inhibitors/*pharmacology; Histone Deacetylases/metabolism; Histones/*drug effects/metabolism; Homeodomain Proteins/metabolism; Hydroxamic Acids/pharmacology; Member 2/*metabolism; Messenger/metabolism; Nuclear Receptor Subfamily 4; Nurr1; Pitx3; Promoter Regions; Rats; RNA; Transcription Factors/metabolism; Valproate; Valproic Acid/*pharmacology
Creator
An entity primarily responsible for making the resource
Green Ashley L; Zhan Le; Eid Aseel; Zarbl Helmut; Guo Grace L; Richardson Jason R
Description
An account of the resource
The dopamine transporter (DAT) is the key regulator of dopaminergic transmission and is a target of several xenobiotics, including pesticides and pharmacological agents. Previously, we identified a prominent role for histone deacetylases in the regulation of DAT expression. Here, we utilized a rat dopaminergic cell line (N27) to probe the responsiveness of DAT mRNA expression to inhibitors of histone acetylation. Inhibition of histone deacetylases (HDACs) by valproate, butyrate and Trichostatin A led to a 3-10-fold increase in DAT mRNA expression, a 50% increase in protein levels, which were accompanied by increased H3 acetylation levels. To confirm the mechanism of valproate-mediated increase in DAT mRNA, chromatin immunoprecipitation (ChIP) assays were used and demonstrated a significant increase in enrichment of acetylation of histone 3 on lysines 9 and 14 (H3K9/K14ac) in the DAT promoter. Expression of Nurr1 and Pitx3, key regulators of DAT expression, were increased following valproate treatment and Nurr1 binding was enriched in the DAT promoter. Together, these results indicate that histone acetylation and subsequent enhancement of transcription factor binding are plausible mechanisms for DAT regulation by valproate and, perhaps, by other xenobiotics.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.neuropharm.2017.07.020" target="_blank" rel="noreferrer noopener">10.1016/j.neuropharm.2017.07.020</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
Acetylation/drug effects
Animals
Butyrates/pharmacology
Cell Line
Cell Survival/drug effects
Department of Pharmaceutical Sciences
Dopamine Plasma Membrane Transport Proteins/*metabolism
Dopamine transporter
Dopaminergic Neurons/cytology/drug effects/metabolism
Dose-Response Relationship
Drug
Eid Aseel
Epigenesis
Epigenetics
Genetic
Genetic/drug effects
Green Ashley L
Group A
Guo Grace L
HDAC
Histone deacetylase
Histone Deacetylase Inhibitors/*pharmacology
Histone Deacetylases/metabolism
Histones/*drug effects/metabolism
Homeodomain Proteins/metabolism
Hydroxamic Acids/pharmacology
Member 2/*metabolism
Messenger/metabolism
NEOMED College of Pharmacy
Neuropharmacology
Nuclear Receptor Subfamily 4
Nurr1
Pitx3
Promoter Regions
Rats
Richardson Jason R
RNA
Transcription Factors/metabolism
Valproate
Valproic Acid/*pharmacology
Zarbl Helmut
Zhan Le
-
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/10.1038/srep42843" target="_blank" rel="noreferrer noopener">http://doi.org/10.1038/srep42843</a>
Pages
42843–42843
Volume
7
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
Mechanisms of Chinese Medicine Xinmailong's protection against heart failure in pressure-overloaded mice and cultured cardiomyocytes.
Publisher
An entity responsible for making the resource available
Scientific reports
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-02
Subject
The topic of the resource
Animal; Animals; Cardiac/cytology/*drug effects/metabolism; Cell Nucleus/metabolism; Cell Survival/drug effects; Cells; Chinese Herbal/*administration & dosage/pharmacology; Constriction; Cultured; Disease Models; Drugs; Echocardiography; GABA Plasma Membrane Transport Proteins/*metabolism; Gene Expression Regulation/drug effects; Glycogen Synthase Kinase 3 beta/metabolism; Heart Failure/etiology/metabolism/physiopathology/*prevention & control; Humans; MAP Kinase Signaling System/drug effects; Mice; Myocytes; Pathologic; Phosphorylation; Proto-Oncogene Proteins c-akt/metabolism; Rats
Creator
An entity primarily responsible for making the resource
Qi Jianyong; Yu Juan; Tan Yafang; Chen Renshan; Xu Wen; Chen Yanfen; Lu Jun; Liu Qin; Wu Jiashin; Gu Weiwang; Zhang Minzhou
Description
An account of the resource
Patients with heart failure (HF) have high mortality and mobility. Xinmailong (XML) injection, a Chinese Medicine, is clinically effective in treating HF. However, the mechanism of XML's effectiveness on HF was unclear, and thus, was the target of the present study. We created a mouse model of pressure-overload-induced HF with transverse aortic constriction (TAC) surgery and compared among 4 study groups: SHAM (n = 10), TAC (n = 12), MET (metoprolol, positive drug treatment, n = 7) and XML (XML treatment, n = 14). Dynamic changes in cardiac structure and function were evaluated with echocardiography in vivo. In addition, H9C2 rat cardiomyocytes were cultured in vitro and the phosphorylation of ERK1/2, AKT, GSK3beta and protein expression of GATA4 in nucleus were detected with Western blot experiment. The results showed that XML reduced diastolic thickness of left ventricular posterior wall, increased ejection fraction and fraction shortening, so as to inhibit HF at 2 weeks after TAC. Moreover, XML inhibited the phosphorylation of ERK1/2, AKT and GSK3beta, subsequently inhibiting protein expression of GATA4 in nucleus (P \textless 0.001). Together, our data demonstrated that XML inhibited the TAC-induced HF via inactivating the ERK1/2, AKT/GSK3beta, and GATA4 signaling pathway.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1038/srep42843" target="_blank" rel="noreferrer noopener">10.1038/srep42843</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
Animal
Animals
Cardiac/cytology/*drug effects/metabolism
Cell Nucleus/metabolism
Cell Survival/drug effects
Cells
Chen Renshan
Chen Yanfen
Chinese Herbal/*administration & dosage/pharmacology
Constriction
Cultured
Disease Models
Drugs
Echocardiography
GABA Plasma Membrane Transport Proteins/*metabolism
Gene Expression Regulation/drug effects
Glycogen Synthase Kinase 3 beta/metabolism
Gu Weiwang
Heart Failure/etiology/metabolism/physiopathology/*prevention & control
Humans
Liu Qin
Lu Jun
MAP Kinase Signaling System/drug effects
Mice
Myocytes
Pathologic
Phosphorylation
Proto-Oncogene Proteins c-akt/metabolism
Qi Jianyong
Rats
Scientific reports
Tan Yafang
Wu Jiashin
Xu Wen
Yu Juan
Zhang Minzhou
-
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/10.1159/000493225" target="_blank" rel="noreferrer noopener">http://doi.org/10.1159/000493225</a>
Pages
932–946
Issue
3
Volume
49
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
Butein Activates Autophagy Through AMPK/TSC2/ULK1/mTOR Pathway to Inhibit IL-6 Expression in IL-1beta Stimulated Human Chondrocytes.
Publisher
An entity responsible for making the resource available
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Date
A point or period of time associated with an event in the lifecycle of the resource
2018
2018
Subject
The topic of the resource
AMP-Activated Protein Kinases/metabolism; AMPK; Articular/cytology/pathology; Autophagy; Autophagy-Related Protein 5/antagonists & inhibitors/genetics/metabolism; Autophagy-Related Protein-1 Homolog/metabolism; Autophagy/*drug effects; Butein; Cartilage; Cell Survival/drug effects; Cells; Chalcones/*pharmacology; Chondrocytes/cytology/drug effects/metabolism; Cultured; Humans; Inflammation; Interleukin-1beta/*pharmacology; Interleukin-6/genetics/*metabolism; Intracellular Signaling Peptides and Proteins/metabolism; mTOR; Osteoarthritis; Osteoarthritis/metabolism/pathology; Phosphorylation/drug effects; Reactive Oxygen Species/metabolism; RNA; RNA Interference; Signal Transduction/*drug effects; Small Interfering/metabolism; TOR Serine-Threonine Kinases/metabolism; TSC2; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins/metabolism; ULK1
Creator
An entity primarily responsible for making the resource
Ansari Mohammad Y; Ahmad Nashrah; Haqqi Tariq M
Description
An account of the resource
BACKGROUND/AIMS: Butein (2',3,4,4'-Tetrahydroxychalcone), a polyphenol produced by several plants including Butea monoserpma, has been reported to exert potent anti-inflammatory activity but the mechanism remains unknown. In the present work we investigated the mechanism of Butein-mediated suppression of IL-6 expression in normal and human osteoarthritis (OA) chondrocytes under pathological conditions. METHODS: Expression level of interleukin-6 (IL-6) protein in OA cartilage was analyzed by immunohistochemistry using a validated antibody. Chondrocytes derived from normal or OA cartilage by enzymatic digestion were pretreated with Butein followed by stimulation with interleukin-1beta (IL-1beta) and the levels of IL-6 mRNA were quantified by TaqMan assay and the protein levels were measured by Western immunoblotting. Autophagy activation was determined by Western blotting and confocal microscopy. Autophagy was inhibited by siRNA mediated knockdown of ATG5. RESULTS: Expression of IL-6 protein was high in the OA cartilage compared to smooth cartilage from the same patient. OA chondrocytes and cartilage explants stimulated with IL-1beta showed high level expression of IL-6 mRNA and protein. Butein increased the phosphorylation of AMPKalphaThr-172, TSC2Ser-1387 and ULK1Ser-317 and inhibited the phosphorylation of mTORSer-2448 and its downstream target p70S6K and increased autophagy flux that correlated with the suppression of the IL-1beta mediated expression of IL-6 in normal and OA chondrocytes. In OA chondrocytes with siRNA-mediated knockdown of ATG5 expression, treatment with Butein failed to activate autophagy and abrogated the suppression of IL-1beta induced IL-6 expression. CONCLUSION: Our findings demonstrate for the first time that Butein activate autophagy in OA chondrocytes via AMPK/TSC2/ULK1/mTOR pathway. Additionally, activation of autophagy was essential to block the IL-1beta-induced expression of IL-6 in OA chondrocytes. These data support further studies to evaluate the use of Butein or compounds derived from it for the management of OA.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1159/000493225" target="_blank" rel="noreferrer noopener">10.1159/000493225</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).
2018
Ahmad Nashrah
AMP-Activated Protein Kinases/metabolism
AMPK
Ansari Mohammad Y
Articular/cytology/pathology
Autophagy
Autophagy-Related Protein 5/antagonists & inhibitors/genetics/metabolism
Autophagy-Related Protein-1 Homolog/metabolism
Autophagy/*drug effects
Butein
Cartilage
Cell Survival/drug effects
Cells
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Chalcones/*pharmacology
Chondrocytes/cytology/drug effects/metabolism
Cultured
Department of Anatomy & Neurobiology
Haqqi Tariq M
Humans
Inflammation
Interleukin-1beta/*pharmacology
Interleukin-6/genetics/*metabolism
Intracellular Signaling Peptides and Proteins/metabolism
mTOR
NEOMED College of Medicine
Osteoarthritis
Osteoarthritis/metabolism/pathology
Phosphorylation/drug effects
Reactive Oxygen Species/metabolism
RNA
RNA Interference
Signal Transduction/*drug effects
Small Interfering/metabolism
TOR Serine-Threonine Kinases/metabolism
TSC2
Tuberous Sclerosis Complex 2 Protein
Tumor Suppressor Proteins/metabolism
ULK1
-
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/10.1166/jbn.2012.1361" target="_blank" rel="noreferrer noopener">http://doi.org/10.1166/jbn.2012.1361</a>
Pages
161–171
Issue
1
Volume
8
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
Antitumor effect of novel gallium compounds and efficacy of nanoparticle-mediated gallium delivery in lung cancer.
Publisher
An entity responsible for making the resource available
Journal of biomedical nanotechnology
Date
A point or period of time associated with an event in the lifecycle of the resource
2012
2012-02
Subject
The topic of the resource
Antineoplastic Agents/*administration & dosage/chemistry/pharmacokinetics; Biocompatible Materials/administration & dosage/chemistry/pharmacokinetics; Cell Line; Cell Survival/drug effects; Coordination Complexes/*administration & dosage/chemistry/pharmacokinetics; Drug Carriers/administration & dosage/chemistry; Drug Stability; Endocytosis/drug effects; Gallium/*administration & dosage/chemistry/pharmacokinetics; Hemolysis/drug effects; Humans; Lung Neoplasms/*drug therapy/metabolism; Materials Testing; Membrane Potential; Mitochondrial/drug effects; Nanoparticles/*administration & dosage/chemistry; Particle Size; Platelet Aggregation/drug effects; Reactive Oxygen Species/metabolism; Transferrin/chemistry/pharmacology; Tumor
Creator
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Wehrung Daniel; Oyewumi Moses O
Description
An account of the resource
The widespread application of gallium (Ga) in cancer therapy has been greatly hampered by lack of specificity resulting in poor tumor accumulation and retention. To address the challenge, two lipophilic gallium (III) compounds (gallium hexanedione; GaH and gallium acetylacetonate; GaAcAc) were synthesized and antitumor studies were conducted in human lung adenocarcinoma (A549) cells. Nanoparticles (NPs) containing various concentrations of the Ga compounds were prepared using a binary mixture of Gelucire 44/14 and cetyl alcohol as matrix materials. NPs were characterized based on size, morphology, stability and biocompatibility. Antitumor effects of free or NP-loaded Ga compounds were investigated based on cell viability, production of reactive oxygen species and reduction of mitochondrial potential. Compared to free Ga compounds, cytotoxicity of NP-loaded Ga (5-150 microg/ml) was less dependent on concentration and incubation time (exposure) with A549 cells. NP-mediated delivery (5-150 microg Ga/ml) enhanced antitumor effects of Ga compounds and the effect was pronounced at: (i) shorter incubation times; and (ii) at low concentrations of gallium (approximately 50 microg/ml) (p \textless 0.0006). Additional studies showed that
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1166/jbn.2012.1361" target="_blank" rel="noreferrer noopener">10.1166/jbn.2012.1361</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).
2012
Antineoplastic Agents/*administration & dosage/chemistry/pharmacokinetics
Biocompatible Materials/administration & dosage/chemistry/pharmacokinetics
Cell Line
Cell Survival/drug effects
Coordination Complexes/*administration & dosage/chemistry/pharmacokinetics
Department of Pharmaceutical Sciences
Drug Carriers/administration & dosage/chemistry
Drug Stability
Endocytosis/drug effects
Gallium/*administration & dosage/chemistry/pharmacokinetics
Hemolysis/drug effects
Humans
Journal of biomedical nanotechnology
Lung Neoplasms/*drug therapy/metabolism
Materials Testing
Membrane Potential
Mitochondrial/drug effects
Nanoparticles/*administration & dosage/chemistry
NEOMED College of Pharmacy
Oyewumi Moses O
Particle Size
Platelet Aggregation/drug effects
Reactive Oxygen Species/metabolism
Transferrin/chemistry/pharmacology
Tumor
Wehrung Daniel
-
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.
Pages
460–464
Volume
737
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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Monoamine-activated alpha 2-macroglobulin inhibits neurite outgrowth, survival, choline acetyltransferase, and dopamine concentration of neurons by blocking neurotrophin-receptor (trk) phosphorylation and signal transduction.
Publisher
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Annals of the New York Academy of Sciences
Date
A point or period of time associated with an event in the lifecycle of the resource
1994
1994-09
Subject
The topic of the resource
Humans; Animals; Cell Survival/drug effects; Phosphorylation/drug effects; Signal Transduction/*drug effects; Infant; Neurons/physiology; Rats; Species Specificity; Choline O-Acetyltransferase/metabolism; Dopamine/metabolism; alpha-Macroglobulins/*pharmacology; Biogenic Monoamines/*pharmacology; Neurites/physiology; Prosencephalon/cytology/*physiology; Receptor Protein-Tyrosine Kinases/*drug effects; Newborn; Receptors; Nerve Growth Factor/*drug effects
Creator
An entity primarily responsible for making the resource
Koo P H; Liebl D J; Qiu W S; Hu Y Q; Dluzen D E
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).
1994
alpha-Macroglobulins/*pharmacology
Animals
Annals of the New York Academy of Sciences
Biogenic Monoamines/*pharmacology
Cell Survival/drug effects
Choline O-Acetyltransferase/metabolism
Dluzen D E
Dopamine/metabolism
Hu Y Q
Humans
Infant
Koo P H
Liebl D J
Nerve Growth Factor/*drug effects
Neurites/physiology
Neurons/physiology
Newborn
Phosphorylation/drug effects
Prosencephalon/cytology/*physiology
Qiu W S
Rats
Receptor Protein-Tyrosine Kinases/*drug effects
Receptors
Signal Transduction/*drug effects
Species Specificity