ArticleThe Journal of biological chemistry2014
A redox-resistant sirtuin-1 mutant protects against hepatic metabolic and oxidant stress.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 67 citations in OpenAlex.
- Epigenetic regulation of the respiratory chain by a mitochondrial distress-related redox signal.Frontiers in cell and developmental biology · 2025Article
- Molecular mechanisms underlying methotrexate-induced intestinal injury and protective strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Inhibition of Sirtuin Deacylase Activity by Peroxynitrite.Biochemistry · 2024Article
- Drivers of cardiovascular disease in metabolic dysfunction-associated steatotic liver disease: the threats of oxidative stress.Frontiers in cardiovascular medicine · 2024Review
- Chemoproteomic strategy identified p120-catenin glutathionylation regulates E-cadherin degradation and cell migration.Cell chemical biology · 2023Article
- Thioredoxin/Glutaredoxin Systems and Gut Microbiota in NAFLD: Interplay, Mechanism, and Therapeutical Potential.Antioxidants (Basel, Switzerland) · 2023Review
- Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Role of Post-translational Modification of Silent Mating Type Information Regulator 2 Homolog 1 in Cancer and Other Disorders.Journal of cancer prevention · 2022Review
- Heterozygous Loss of KRIT1 in Mice Affects Metabolic Functions of the Liver, Promoting Hepatic Oxidative and Glycative Stress.International journal of molecular sciences · 2022Article
- Sperm cryopreservation and DNA methylation: possible implications for ART success and the health of offspring.Journal of assisted reproduction and genetics · 2022Review
- Administration of Glutaredoxin-1 Attenuates Liver Fibrosis Caused by Aging and Non-Alcoholic Steatohepatitis.Antioxidants (Basel, Switzerland) · 2022Article
- Sirtuins and Sepsis: Cross Talk between Redox and Epigenetic Pathways.Antioxidants (Basel, Switzerland) · 2021Review
- The selective degradation of sirtuins via macroautophagy in the MPPCell death discovery · 2021Article
- Oxidized GAPDH transfers S-glutathionylation to a nuclear protein Sirtuin-1 leading to apoptosis.Free radical biology & medicine · 2021Article
- Glutaredoxin: Discovery, redox defense and much more.Redox biology · 2021Review
- Sirtuin Oxidative Post-translational Modifications.Frontiers in physiology · 2021Review
- Alcohol Binge Drinking Selectively Stimulates Protein S-Glutathionylation in Aorta and Liver ofFrontiers in cardiovascular medicine · 2021Article
- Redox Regulation by Protein S-Glutathionylation: From Molecular Mechanisms to Implications in Health and Disease.International journal of molecular sciences · 2020Review
- Role of Glutaredoxin-1 and Glutathionylation in Cardiovascular Diseases.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Sirtuin-1 (SirT1), a member of the NAD(+)-dependent class III histone deacetylase family, is inactivated in vitro by oxidation of critical cysteine thiols. In a model of metabolic syndrome, SirT1 activation attenuated apoptosis of hepatocytes and improved liver function including lipid metabolism. We show in SirT1-overexpressing HepG2 cells that oxidants (nitrosocysteine and hydrogen peroxide) or metabolic stress (high palmitate and high glucose) inactivated SirT1 by reversible oxidative post-translational modifications (OPTMs) on three cysteines. Mutating these oxidation-sensitive cysteines to serine preserved SirT1 activity and abolished reversible OPTMs. Overexpressed mutant SirT1 maintained deacetylase activity and attenuated proapoptotic signaling, whereas overexpressed wild type SirT1 was less protective in metabolically or oxidant-stressed cells. To prove that OPTMs of SirT1 are glutathione (GSH) adducts, glutaredoxin-1 was overexpressed to remove this modification. Glutaredoxin-1 overexpression maintained endogenous SirT1 activity and prevented proapoptotic signaling in metabolically stressed HepG2 cells. The in vivo significance of oxidative inactivation of SirT1 was investigated in livers of high fat diet-fed C57/B6J mice. SirT1 deacetylase activity was decreased in the absence of changes in SirT1 expression and associated with a marked increase in OPTMs. These results indicate that glutathione adducts on specific SirT1 thiols may be responsible for dysfunctional SirT1 associated with liver disease in metabolic syndrome.
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