Role of peroxisome proliferator-activated receptor-alpha in fasting-mediated oxidative stress
Aldehyde dehydrogenase; Biochemistry & Molecular Biology; differential expression; dismutase; Endocrinology & Metabolism; Fasting; fatty-acid oxidation; glutathione-s-transferase; hepatic steatosis; Lipid peroxidation; Lipid peroxidation; liver; manganese-superoxide-dismutase; mitochondrial aldehyde dehydrogenase; nitric-oxide; Null mice; oxidative stress; PPAR-alpha; PPAR-alpha; Protein nitration; Protein oxidation; rat-liver; Steatosis; Superoxide
The peroxisome proliferator-activated receptor-alpha (PPAR alpha) regulates lipid homeostasis, particularly in the liver. This study was aimed at elucidating the relationship between hepatosteatosis and oxidative stress during fasting. Fasted Ppara-null mice exhibited marked hepatosteatosis, which was associated with elevated levels of lipid peroxidation, nitric oxide synthase activity, and hydrogen peroxide accumulation. Total glutathione (GSH), mitochondrial GSH, and the activities of major antioxidant enzymes were also lower in the fasted Ppara-null mice. Consequently, the number and extent of nitrated proteins were markedly increased in the fasted Ppara-null mice, although high levels of protein nitration were still detected in the fed Ppara-null mice while many oxidatively modified proteins were only found in the fasted Ppara-null mice. However, the role of inflammation in increased oxidative stress in the fasted Ppara-null mice was minimal based on the similar levels of tumor necrosis factor-alpha change in all groups. These results with increased oxidative stress observed in the fasted Ppara-null mice compared with other groups demonstrate a role for PPAR alpha in fasting-mediated oxidative stress and that inhibition of PPAR alpha functions may increase the susceptibility to oxidative damage in the presence of another toxic agent. Published by Elsevier Inc.
Abdelmegeed M A; Moon K H; Hardwick J P; Gonzalez F J; Song B J
Free Radical Biology and Medicine
2009
2009-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.freeradbiomed.2009.06.017" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2009.06.017</a>
Enhanced ethanol catabolism in orphan nuclear receptor SHP-null mice.
*acetaldehyde dehydrogenase; *alcoholic fatty liver disease; *inflammation; *small heterodimer partner; Acetates/blood; Alcoholic/genetics/*metabolism; Aldehyde Dehydrogenase; Animals; Cytoplasmic and Nuclear/deficiency/*genetics/metabolism; Ethanol/blood/*metabolism/toxicity; Inbred C57BL; Lipid Peroxidation; Liver Diseases; Liver/drug effects/metabolism; Male; Mice; Mitochondrial/genetics/metabolism; PPAR gamma/genetics/metabolism; Receptors
Deficiency of the orphan nuclear hormone receptor small heterodimer partner (SHP, NR0B2) protects mice from diet-induced hepatic steatosis, in part, via repression of peroxisome proliferator-activated receptor (PPAR)-gamma2 (Pparg2) gene expression. Alcoholic fatty liver diseases (AFLD) share many common pathophysiological features with non-AFLD. To study the role of SHP and PPARgamma2 in AFLD, we used a strategy of chronic ethanol feeding plus a single binge ethanol feeding to challenge wild-type (WT) and SHP-null (SHP(-/-)) mice with ethanol. The ethanol feeding induced liver fat accumulation and mRNA expression of hepatic Pparg2 in WT mice, which suggests that a high level of PPARgamma2 is a common driving force for fat accumulation induced by ethanol or a high-fat diet. Interestingly, ethanol-fed SHP(-/-) mice displayed hepatic fat accumulation similar to that of ethanol-fed WT mice, even though their Pparg2 expression level remained lower. Mortality of SHP(-/-) mice after ethanol binge feeding was significantly reduced and their acetaldehyde dehydrogenase (Aldh2) mRNA level was higher than that of their WT counterparts. After an intoxicating dose of ethanol, SHP(-/-) mice exhibited faster blood ethanol clearance and earlier wake-up time than WT mice. Higher blood acetate, the end product of ethanol metabolism, and lower acetaldehyde levels were evident in the ethanol-challenged SHP(-/-) than WT mice. Ethanol-induced inflammatory responses and lipid peroxidation were also lower in SHP(-/-) mice. The current data show faster ethanol catabolism and extra fat storage through conversion of acetate to acetyl-CoA before its release into the circulation in this ethanol-feeding model in SHP(-/-) mice.
Park Jung Eun; Lee Mikang; Mifflin Ryan; Lee Yoon-Kwang
American journal of physiology. Gastrointestinal and liver physiology
2016
2016-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajpgi.00343.2015" target="_blank" rel="noreferrer noopener">10.1152/ajpgi.00343.2015</a>
4-Hydroxynonenal dependent alteration of TRPV1-mediated coronary microvascular signaling.
*4-Hydroxynonenal; *Coronary regulation; *Lipid peroxidation; *Post-translational modification; *Protein Processing; *Reactive oxygen species; *Signal Transduction; *TRPV1; Action Potentials/drug effects; Aldehydes/antagonists & inhibitors/metabolism/*pharmacology; Animal; Animals; Blood Flow Velocity; Calcium Signaling/drug effects; Capsaicin/*pharmacology; Cardiovascular Agents/*pharmacology; Coronary Circulation/drug effects; Coronary Vessels/metabolism/physiopathology; Cysteine/genetics/metabolism; Diabetes Mellitus/drug therapy/*metabolism/physiopathology; Disease Models; Femoral Artery/metabolism/physiopathology; HEK293 Cells; Humans; Inbred C57BL; Lipid Peroxidation; Male; Mice; Patch-Clamp Techniques; Post-Translational; TRPV Cation Channels/genetics/*metabolism; Vasodilation/drug effects
We demonstrated previously that TRPV1-dependent regulation of coronary blood flow (CBF) is disrupted in diabetes. Further, we have shown that endothelial TRPV1 is differentially regulated, ultimately leading to the inactivation of TRPV1, when exposed to a prolonged pathophysiological oxidative environment. This environment has been shown to increase lipid peroxidation byproducts including
DelloStritto Daniel J; Sinharoy Pritam; Connell Patrick J; Fahmy Joseph N; Cappelli Holly C; Thodeti Charles K; Geldenhuys Werner J; Damron Derek S; Bratz Ian N
Free radical biology & medicine
2016
2016-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.freeradbiomed.2016.09.021" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2016.09.021</a>
Synergistic antitumour activity of vitamins C and K3 against human prostate carcinoma cell lines.
Adenosine Triphosphate/biosynthesis; Antineoplastic Agents/*pharmacology/toxicity; Antineoplastic Combined Chemotherapy Protocols/pharmacology; Ascorbic Acid/*pharmacology/toxicity; Carcinoma/*metabolism; Catalase/pharmacology; Cultured; DNA; Humans; Hydrogen Peroxide/metabolism; Lipid Peroxidation; Male; Neoplasm Proteins/biosynthesis; Neoplasm/biosynthesis; Prostatic Neoplasms/*metabolism; Sulfhydryl Compounds/analysis; Tumor Cells; Vitamin K/*pharmacology/toxicity
Vitamins C, K3 (VC, VK3) and a VC/VK3 combination with a VC:VK3 ratio of 100:1 were assayed for their antitumour activity against two human prostatic carcinoma cell lines. Co-administration of the vitamins enhanced the antitumour activity 5- to 20-fold even with a 1 h exposure time. While exogenous catalase destroyed the antitumour activity, hydrogen peroxide-induced lipid peroxidation was negligible. Analysis of cellular ATP and thiol levels as well as DNA and protein synthesis revealed: a transient increase in ATP production, a decrease in DNA synthesis, an increase in protein synthesis and a decrease in thiol levels. These results suggested that the increased cytotoxicity of the vitamin combination was due to redox cycling and increased oxidative stress.
Venugopal M; Jamison J M; Gilloteaux J; Koch J A; Summers M; Hoke J; Sowick C; Summers J L
Cell biology international
1996
1996-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/cbir.1996.0102" target="_blank" rel="noreferrer noopener">10.1006/cbir.1996.0102</a>