title: Tissue hypoxia activates JNK in the liver during hemorrhagic shock.
abstract: The earliest signaling pathways responsible for initiating the systemic response to hemorrhagic shock (HS) remain poorly characterized. We have investigated the involvement of the mitogen-activated protein (MAP) kinase C-JUN N-terminal kinase (JNK) and its activation in the liver as an early response to tissue hypoxia soon after the initiation of hemorrhage. In the present studies, hemorrhage of mice to 25 mmHg for 30 min resulted in a significant (2.1-fold) increase in JNK phosphorylation within the liver. Results were similar in rats hemorrhaged to 40 mmHg for 1 h. Hypoxia alone, replicated by warm isolated hepatic ischemia in vivo or hepatocytes cultured under 1% oxygen, also resulted in JNK phosphorylation. Finally, preservation of tissue perfusion and oxygenation by pretreatment with a blood-soluble drag-reducing polymer (DRP) in the rat HS model prevented phosphorylation of JNK in the liver. These results identify tissue hypoxia as a key factor in activating early signaling events in the liver following hemorrhage, as measured by JNK phosphorylation.
authors.affiliation: Department of General Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15260, USA. mccloskeyc@msc.upmc.edu
authors.forename: Carol A
authors.initials: CA
authors.lastname: McCloskey
authors.forename: Marina V
authors.initials: MV
authors.lastname: Kameneva
authors.forename: Arkady
authors.initials: A
authors.lastname: Uryash
authors.forename: David J
authors.initials: DJ
authors.lastname: Gallo
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009061:Mouth Mucosa / Q000098:blood supply; D010766:Phosphorylation; D011092:Polyethylene Glycols / Q000494:pharmacology; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D013501:Surface-Active Agents / Q000494:pharmacology; D014655:Vascular Resistance
chemical_list: D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D048031:JNK Mitogen-Activated Protein Kinases