title: Mitogen-activated protein kinases mediate heat shock-induced delayed protection in mouse heart.
abstract: We determined the role of p38 mitogen-activated protein kinase (MAPK), 72-kDa heat shock protein (HSP72), and antioxidant enzymes in whole body heat stress (HS)-induced cardioprotection in mouse hearts. Adult male mice were treated with either HS or anesthesia only. At 0.5, 48, 72, or 120 h later, the hearts were subjected to 20 min of global ischemia and 30 min of reperfusion in Langendorff mode. A significant protection against ischemia-reperfusion injury was observed 48 h after HS as demonstrated by: 1) reduction in infarct size; 2) decrease in leakage of lactate dehydrogenase; and 3) enhanced postischemic ventricular contractile function. No such protection was observed at other post-HS time points. HS caused an ~25% increase in phosphorylated c-Jun NH2-terminal kinase (JNK) but not p38 MAPK in the heart during the first 2-h post-HS time period. Cardioprotection was abolished by the MAPK inhibitor SB-203580, which also partially suppressed the HS-induced JNK phosphorylation. The protective effect was associated with a two- to threefold increase in HSP72 protein accumulation, but not antioxidant enzyme activities (catalase and Cu/Zn and Mn SOD) in the myocardium. Although HSP72 levels remained high 72 h after HS, the cardioprotection had already disappeared. We conclude that HS induces a transient delayed cardioprotection at 48 h after thermal stress in mice which appears to be mediated via a MAPK-signaling pathway.
authors.affiliation: Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tekin
authors.forename: L
authors.initials: L
authors.lastname: Xi
authors.forename: T
authors.initials: T
authors.lastname: Zhao
authors.forename: M I
authors.initials: MI
authors.lastname: Tejero-Taldo
authors.forename: S
authors.initials: S
authors.lastname: Atluri
authors.forename: R C
authors.initials: RC
authors.lastname: Kukreja
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018882:Heat Stress Disorders / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580