title: Protective role of c-Jun N-terminal kinase 2 in acetaminophen-induced liver injury.
abstract: Recent studies in mice suggest that stress-activated c-Jun N-terminal protein kinase 2 (JNK2) plays a pathologic role in acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure (ALF). In contrast, we present evidence that JNK2 can have a protective role against AILI. When male C57BL/6J wild type (WT) and JNK2(-/-) mice were treated with 300mg APAP/kg, 90% of JNK2(-/-) mice died of ALF compared to 20% of WT mice within 48h. The high susceptibility of JNK2(-/-) mice to AILI appears to be due in part to deficiencies in hepatocyte proliferation and repair. Therefore, our findings are consistent with JNK2 signaling playing a protective role in AILI and further suggest that the use of JNK inhibitors as a potential treatment for AILI, as has been recommended by other investigators, should be reconsidered.
authors.affiliation: Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-1760, USA. bourdim@nih.gov
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bourdi
authors.forename: Midhun C
authors.initials: MC
authors.lastname: Korrapati
authors.forename: Mala
authors.initials: M
authors.lastname: Chakraborty
authors.forename: Steven B
authors.initials: SB
authors.lastname: Yee
authors.forename: Lance R
authors.initials: LR
authors.lastname: Pohl
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000201:enzymology* / Q000235:genetics; D008115:Liver Regeneration / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000502:physiology*
chemical_list: D018712:Analgesics, Non-Narcotic; D056741:Cyclin D; D016213:Cyclins; D000082:Acetaminophen; D048056:Mitogen-Activated Protein Kinase 9