ArticleHepatology (Baltimore, Md.)2014
Protein kinase C (PKC) participates in acetaminophen hepatotoxicity through c-jun-N-terminal kinase (JNK)-dependent and -independent signaling pathways.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 86 citations in OpenAlex.
- Post-Translational Modifications of NTCP: A Regulatory Nexus for Bile Acid Transport and HBV Entry.Biomedicines · 2026Review
- Peli3 ablation ameliorates acetaminophen-induced liver injury through inhibition of GSK3β phosphorylation and mitochondrial translocation.Experimental & molecular medicine · 2023Article
- Protein Kinase C Inhibitors Reduce SARS-CoV-2 Replication in Cultured Cells.Microbiology spectrum · 2022Article
- Ameliorative effect of Lactobacillus rhamnosus GG on acetaminophen-induced hepatotoxicity via PKC/Nrf2/PGC-1α pathway.Journal, genetic engineering & biotechnology · 2022Article
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- IL-22-mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury.Clinical and translational medicine · 2021Article
- Acetaminophen Test Battery (ATB): A Comprehensive Method to Study Acetaminophen-Induced Acute Liver Injury.Gene expression · 2020Review
- Aescin and diosmin each alone or in low dose- combination ameliorate liver damage induced by carbon tetrachloride in rats.BMC research notes · 2020Article
- Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury.Theranostics · 2020Article
- Forskolin and Phorbol 12-myristate 13-acetate modulates the expression pattern of AP-1 factors and cell cycle regulators in estrogen-responsive MCF-7 cells.Genes & diseases · 2019Article
- Diverse Functions of Autophagy in Liver Physiology and Liver Diseases.International journal of molecular sciences · 2019Review
- Corilagin alleviates acetaminophen-induced hepatotoxicity via enhancing the AMPK/GSK3β-Nrf2 signaling pathway.Cell communication and signaling : CCS · 2019Article
- GADD45α alleviates acetaminophen-induced hepatotoxicity by promoting AMPK activation.Cellular and molecular life sciences : CMLS · 2019Article
- Hepatoprotective Effect of Baicalein Against Acetaminophen-Induced Acute Liver Injury in Mice.Molecules (Basel, Switzerland) · 2018Article
- Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions.Redox biology · 2018Review
- Dihydroquercetin ameliorated acetaminophen-induced hepatic cytotoxicity via activating JAK2/STAT3 pathway and autophagy.Applied microbiology and biotechnology · 2018Article
- Review
- Mitochondrial-Lysosomal Axis in Acetaminophen Hepatotoxicity.Frontiers in pharmacology · 2018Review
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6 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledThis study examines the role of protein kinase C (PKC) and AMP-activated kinase (AMPK) in acetaminophen (APAP) hepatotoxicity. Treatment of primary mouse hepatocytes with broad-spectrum PKC inhibitors (Ro-31-8245, Go6983), protected against APAP cytotoxicity despite sustained c-jun-N-terminal kinase (JNK) activation. Broad-spectrum PKC inhibitor treatment enhanced p-AMPK levels and AMPK regulated survival-energy pathways including autophagy. AMPK inhibition by compound C or activation using an AMPK activator oppositely modulated APAP cytotoxicity, suggesting that p-AMPK and AMPK regulated energy survival pathways, particularly autophagy, play a critical role in APAP cytotoxicity. Ro-31-8245 treatment in mice up-regulated p-AMPK levels, increased autophagy (i.e., increased LC3-II formation, p62 degradation), and protected against APAP-induced liver injury, even in the presence of sustained JNK activation and translocation to mitochondria. In contrast, treatment of hepatocytes with a classical PKC inhibitor (Go6976) protected against APAP by inhibiting JNK activation. Knockdown of PKC-α using antisense (ASO) in mice also protected against APAP-induced liver injury by inhibiting JNK activation. APAP treatment resulted in PKC-α translocation to mitochondria and phosphorylation of mitochondrial PKC substrates. JNK 1 and 2 silencing in vivo decreased APAP-induced PKC-α translocation to mitochondria, suggesting PKC-α and JNK interplay in a feed-forward mechanism to mediate APAP-induced liver injury.
conclusionPKC-α and other PKC(s) regulate death (JNK) and survival (AMPK) proteins, to modulate APAP-induced liver injury.
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