ArticleScientific reports2016
Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
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- Exercise-activated hepatic autophagy combined with silymarin is associated with suppression of apoptosis in rats subjected to dexamethasone induced- fatty liver damage.Molecular biology reports · 2024Article
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- Procyanidin A1 alleviates DSS-induced ulcerative colitis via regulating AMPK/mTOR/p70S6K-mediated autophagy.Journal of physiology and biochemistry · 2022Article
- 5-O-Demethylnobiletin Alleviates CClInternational journal of molecular sciences · 2021Article
- Identification and Analysis of Potential Autophagy-Related Biomarkers in Endometriosis by WGCNA.Frontiers in molecular biosciences · 2021Article
- Deficiency of miR-208a Exacerbates CClHepatology communications · 2020Article
- Autophagy regulation is an effective strategy to improve the prognosis of chemically induced acute liver injury based on experimental studies.Journal of cellular and molecular medicine · 2020Review
- A Cell's Fate: An Overview of the Molecular Biology and Genetics of Apoptosis.International journal of molecular sciences · 2019Review
- Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis.Cell death & disease · 2018Article
- Role of autophagy in the pathogenesis of inflammatory bowel disease.World journal of gastroenterology · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury.
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