ArticleCell & bioscience2020
Sirt6 opposes glycochenodeoxycholate-induced apoptosis of biliary epithelial cells through the AMPK/PGC-1α pathway.
Article in Cell & bioscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Association between anion gap trajectories and mortality in patients with acute cholangitis: a cohort study.Scientific reports · 2026Article
- Regulation of bile acids homeostasis: a feasible and versatile way to treat or diagnose liver disorders.Frontiers in nutrition · 2026Review
- Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy.Frontiers in pharmacology · 2026Review
- SIRT6 Relieves Acute Lung Injury by Enhancing PGC-1α Expression and Improving Mitochondrial Function.Current molecular medicine · 2026Article
- The medial septal-medial habenula cholinergic circuit: A new mechanism of exercise improving cognitive function in AD mice.Journal of sport and health science · 2025Article
- The Influence of Sirtuin 6 on Chondrocyte Senescence in Osteoarthritis Under Aging: Focusing on Mitochondrial Dysfunction and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Review
- Hepatic SIRT6 protects against cholestatic liver disease primarilyJournal of biomedical research · 2024Article
- Exercise and nutrition benefit skeletal muscle: From influence factor and intervention strategy to molecular mechanism.Sports medicine and health science · 2024Review
- USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6.Molecular neurobiology · 2024Article
- KLF6 alleviates hepatic ischemia-reperfusion injury by inhibiting autophagy.Cell death & disease · 2023Article
- SIRT6 regulates SREBP1c-induced glucolipid metabolism in liver and pancreas via the AMPKα-mTORC1 pathway.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Roles of SIRT6 in kidney disease: a novel therapeutic target.Cellular and molecular life sciences : CMLS · 2021Article
- Vitexin ameliorates glycochenodeoxycholate-induced hepatocyte injury through SIRT6 and JAK2/STAT3 pathways.Iranian journal of basic medical sciences · 2021Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInduction of biliary epithelial cell apoptosis by toxic bile acids is involved in the development of cholestatic disease, but the underlying molecular mechanism is not clear. The purpose of this study was to investigate the molecular mechanisms involved in Sirt6 protection against the apoptosis of human intrahepatic biliary epithelial cells (HiBEC) induced by the bile acid glycochenodeoxycholate (GCDC).
resultsSirt6 was either overexpressed or knocked down in HiBEC, with or without GCDC pretreatment. The CCK-8 assay was used to assess cell viability and, Hoechst 33258 staining was used to determine apoptotic rate. Mitochondrial DNA (mtDNA) copy number, malondialdehyde (MDA) and reactive oxygen species (ROS) production were detected to evaluate the severity of the mitochondrial dysfunction and oxidative stress. The mRNA and protein levels of PGC-1α, Nrf1, and Nrf2 were analyzed using RT-qPCR and western blot assay. The results showed that Sirt6 opposed GCDC-induced apoptosis in HiBEC via up-regulating PGC-1α expression and stabilizing mtDNA. We used agonists and inhibitors of AMPK to demonstrate that Sirt6 increased PGC-1α expression through the AMPK pathway whereas GCDC had the opposite effect. Finally, western blot, luciferase assay, and co-immunoprecipitation were used to describe a direct interaction and acetylation modification of PGC-1α by Sirt6.
conclusionOur data illuminated that Sirt6 ameliorated GCDC-induced HiBEC apoptosis by upregulating PGC-1α expression through the AMPK pathway and its deacetylation effect.
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