ArticleThe Journal of clinical investigation2019
Expression of mitochondrial membrane-linked SAB determines severity of sex-dependent acute liver injury.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Epidemiology of drug-related liver injury among the elderly: a systematic review and meta-analysis of incidence, and risk factors.BMC pharmacology & toxicology · 2025Pooled it
- The Association Between Serum Gamma-Glutamyl Transferase and Gastrointestinal Cancer Risk: A Systematic Review and Meta-Analysis.Cancer medicine · 2025Pooled it
- Hepatoprotective effects of resolvin D1 in mice exposed to ethanol and galactosamine.Hepatology communications · 2026Article
- Role of the Plasminogen Activation System in Liver Injury and Repair: Knowns and Known Unknowns.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- SRY mediates male-specific susceptibility to acute liver injury.Cell communication and signaling : CCS · 2025Article
- Asialoglycoprotein receptor 1: a multifaceted receptor in the liver and cardiovascular system.Frontiers in medicine · 2025Review
- Therapeutic liver cell transplantation to treat murine PKU.Journal of inherited metabolic disease · 2024Article
- Hypogonadism and nonalcoholic fatty liver disease.Endocrine · 2024Review
- Hepatic LRP-1 plays an important role in amyloidosis in Alzheimer's disease mice: Potential role in chronic heavy alcohol feeding.Neurobiology of disease · 2024Article
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Mitochondrial P-JNK target, SAB (SH3BP5), in regulation of cell death.Frontiers in cell and developmental biology · 2024Review
- Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice.Frontiers in cell and developmental biology · 2024Article
- Article
- Hepatic pyruvate and alanine metabolism are critical and complementary for maintenance of antioxidant capacity and resistance to oxidative insult.Molecular metabolism · 2023Article
- c-Antioxidants & redox signaling · 2023Article
- Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease.Biomedicines · 2022Review
- Platanosides, a Potential Botanical Drug Combination, Decrease Liver Injury Caused by Acetaminophen Overdose in Mice.Journal of natural products · 2022Review
- Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options.Journal of Zhejiang University. Science. B · 2022Review
- Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis.Cancers · 2022Review
- Hepatic Mitochondrial SAB Deletion or Knockdown Alleviates Diet-Induced Metabolic Syndrome, Steatohepatitis, and Hepatic Fibrosis.Hepatology (Baltimore, Md.) · 2021Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
SH3 domain-binding protein that preferentially associates with Btk (SAB) is an outer-membrane docking protein for JNK-mediated impairment of mitochondrial function. Deletion of Sab in hepatocytes inhibits sustained JNK activation and cell death. The current study demonstrates that an increase in SAB expression enhanced the severity of acetaminophen-induced (APAP-induced) liver injury. Female mice were resistant to liver injury and exhibited markedly decreased hepatic SAB protein expression compared with male mice. The mechanism of SAB repression involved a pathway from ERα to p53 expression that induced miR34a-5p. miR34a-5p targeted the Sab mRNA coding region, thereby repressing SAB expression. Fulvestrant or p53 knockdown decreased miR34a-5p and increased SAB expression in female mice, leading to increased injury from APAP and TNF/galactosamine. In contrast, an ERα agonist increased p53 and miR34a-5p, which decreased SAB expression and hepatotoxicity in male mice. Hepatocyte-specific deletion of miR34a also increased the severity of liver injury in female mice, which was prevented by GalNAc-ASO knockdown of Sab. Similar to mice, premenopausal women expressed elevated levels of hepatic p53 and low levels of SAB, whereas age-matched men expressed low levels of p53 and high levels of SAB, but there was no difference in SAB expression between the sexes in the postmenopausal stage. In conclusion, SAB expression levels determined the severity of JNK-dependent liver injury. Female mice expressed low levels of hepatic SAB protein because of the ERα/p53/miR34a pathway, which repressed SAB expression and accounted for the resistance to liver injury seen in these females.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.