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>
Robust protein nitration contributes to acetaminophen-induced mitochondrial dysfunction and acute liver injury
3-Nitrotyrosine; Acetaminophen; Acute liver injury; Biochemistry & Molecular Biology; covalent binding; CYP2E1; Endocrinology & Metabolism; Free radicals; immunohistochemical localization; induced hepatotoxicity; knockout mice; Mitochondrial dysfunction; mouse-liver; n-acetylcysteine; n-acetylcysteine; nitration; nitric-oxide synthase; oxidative stress; protein; superoxide-dismutase; terminal kinase
Acetaminophen (APAP), a widely used analgesic/antipyretic agent, can cause liver injury through increased nitrative stress, leading to protein nitration. However, the identities of nitrated proteins and their roles in hepatotoxicity are poorly understood. Thus, we aimed at studying the mechanism of APAP-induced hepatotoxicity by systematic identification and characterization of nitrated proteins in the absence or presence of an antioxidant, N-acetylcysteine (NAC). The levels of nitrated proteins markedly increased at 2 h in mice exposed to a single APAP dose (350 mg/kg ip), which caused severe liver necrosis at 24 h. Protein nitration and liver necrosis were minimal in mice exposed to nontoxic 3-hydroxyacetanilide or animals co-treated with APAP and NAC. Mass-spectral analysis of the affinity-purified nitrated proteins identified numerous mitochondrial and cytosolic proteins, including mitochondrial aldehyde dehydrogenase, Mn-superoxide dismutase, glutathione peroxidase, ATP synthase, and 3-ketoacyl-CoA thiolase, involved in antioxidant defense, energy supply, or fatty acid metabolism. Immunoprecipitation followed by immunoblot with anti-3-nitrotyrosine antibody confirmed that the aforementioned proteins were nitrated in APAP-exposed mice but not in NAC-cotreated mice. Consistently, NAC cotreatment significantly restored the suppressed activity of these enzymes. Thus, we demonstrate a new mechanism by which many nitrated proteins with concomitantly suppressed activity promotes APAP-induced mitochondrial dysfunction and hepatotoxicity. Published by Elsevier Inc.
Abdelmegeed M A; Jang S; Banerjee A; Hardwick J P; Song B J
Free Radical Biology and Medicine
2013
2013-07
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.freeradbiomed.2013.02.018" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2013.02.018</a>
Pleiotropic Roles Of Nrf2 As Regulators Of Chondrocyte Apoptosis, Oxidative Stress, Inflammatory Response And Catabolic And Anabolic Pathways In Osteoarthritis
Biochemistry & Molecular Biology; Endocrinology & Metabolism
Khan N M; Haqqi T M
Free Radical Biology and Medicine
2017
2017-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.freeradbiomed.2017.10.300" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2017.10.300</a>
Increased Cysteine Sulfonation Of The Hydrophilic Domain Of Complex I Mediates Mitochondrial Dysfunction In The Post-ischemic Heart
Biochemistry & Molecular Biology; Endocrinology & Metabolism
Kang P T; Chen C L; Lin P; Zhang L W; Chen Y R
Free Radical Biology and Medicine
2017
2017-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.freeradbiomed.2017.10.170" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2017.10.170</a>
Differential Protein Acetylation Mediates Mitochondrial Localization and Pentameric Aggregation of SOD2 in the Murine Heart of SOD2-Tg
Biochemistry & Molecular Biology; Endocrinology & Metabolism
Chen C L; Kang P T; Zhang L W; Chen Y R
Free Radical Biology and Medicine
2016
2016-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.freeradbiomed.2016.10.361" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2016.10.361</a>
Butein: A Plant Derived Small Molecule Activates Autophagy and Suppresses IL-1 beta-Induced Oxidative Stress, Mitochondrial Dysfunction and Inflammatory Response in Human Chondrocytes
Biochemistry & Molecular Biology; Endocrinology & Metabolism
Ansari M Y; Haqqi T M
Free Radical Biology and Medicine
2017
2017-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.freeradbiomed.2017.10.214" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2017.10.214</a>