ArticleBiochimica et biophysica acta2016
Involvement of connexin43 in acetaminophen-induced liver injury.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Iron-related intercellular communication in the liver: Main players and mechanisms.European journal of clinical investigation · 2026Review
- 18-α-glycyrrhetinic acid alleviates oxidative damage in periodontal tissue by modulating the interaction of Cx43 and JNK/NF-κB pathways.Frontiers in pharmacology · 2023Article
- Effects of acute and chronic disease on cell junctions in mouse liver.EXCLI journal · 2023Article
- Expression of connexins and pannexins in diseased human liver.EXCLI journal · 2022Article
- Expression and Functionality of Connexin-Based Channels in Human Liver Cancer Cell Lines.International journal of molecular sciences · 2021Article
- Connexin-Based Channel Activity Is Not Specifically Altered by Hepatocarcinogenic Chemicals.International journal of molecular sciences · 2021Article
- Global Spread of a Local Fire: Transmission of Endoplasmic Reticulum Stress via Connexin 43.Cell metabolism · 2021Article
- Intercellular Transmission of Hepatic ER Stress in Obesity Disrupts Systemic Metabolism.Cell metabolism · 2021Article
- Sensing Acute Cellular Rejection in Liver Transplant Patients Using Liver-Derived Extracellular Particles: A Prospective, Observational Study.Frontiers in immunology · 2021Observational
- Cholestasis Differentially Affects Liver Connexins.International journal of molecular sciences · 2020Article
- A robust bacterial assay for high-throughput screening of human 4-hydroxyphenylpyruvate dioxygenase inhibitors.Scientific reports · 2019Article
- Gadolinium Chloride Restores the Function of the Gap Junctional Intercellular Communication between Hepatocytes in a Liver Injury.International journal of molecular sciences · 2019Article
- Genetic ablation of pannexin1 counteracts liver fibrosis in a chemical, but not in a surgical mouse model.Archives of toxicology · 2018Article
- TAT-Gap19 and Carbenoxolone Alleviate Liver Fibrosis in Mice.International journal of molecular sciences · 2018Article
- The role of connexin and pannexin containing channels in the innate and acquired immune response.Biochimica et biophysica acta. Biomembranes · 2018Review
- Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in mice.Toxicology letters · 2017Article
- Inhibition of connexin hemichannels alleviates non-alcoholic steatohepatitis in mice.Scientific reports · 2017Article
- Inhibition of pannexin1 channels alleviates acetaminophen-induced hepatotoxicity.Archives of toxicology · 2017Article
- The role of gap junctions in inflammatory and neoplastic disorders (Review).International journal of molecular medicine · 2017Review
- Mechanisms of acetaminophen hepatotoxicity and their translation to the human pathophysiology.Journal of clinical and translational research · 2017Article
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsBeing goalkeepers of liver homeostasis, gap junctions are also involved in hepatotoxicity. However, their role in this process is ambiguous, as gap junctions can act as both targets and effectors of liver toxicity. This particularly holds true for drug-induced liver insults. In the present study, the involvement of connexin26, connexin32 and connexin43, the building blocks of liver gap junctions, was investigated in acetaminophen-induced hepatotoxicity.
methodsC57BL/6 mice were overdosed with 300mg/kg body weight acetaminophen followed by analysis of the expression and localization of connexins as well as monitoring of hepatic gap junction functionality. Furthermore, acetaminophen-induced liver injury was compared between mice genetically deficient in connexin43 and wild type littermates. Evaluation of the toxicological response was based on a set of clinically relevant parameters, including protein adduct formation, measurement of alanine aminotransferase activity, cytokines and glutathione.
resultsIt was found that gap junction communication deteriorates upon acetaminophen intoxication in wild type mice, which is associated with a switch in mRNA and protein production from connexin32 and connexin26 to connexin43. The upregulation of connexin43 expression is due, at least in part, to de novo production by hepatocytes. Connexin43-deficient animals tended to show increased liver cell death, inflammation and oxidative stress in comparison with wild type counterparts.
conclusionThese results suggest that hepatic connexin43-based signaling may protect against acetaminophen-induced liver toxicity.
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