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.

Cardioprotection mediated by sphingosine-1-phosphate and ganglioside GM-1 in wild-type and PKCε knockout mouse hearts

“…In this connection, it should be noted that a large infarct area resulted from a relatively short ischemic time of 20 min and reperfusion time of 30 min. In an identical model using a different a strain of mouse, Tekin et al (28) recently reported that after 20 min of ischemia and 30 min of reperfusion, infarct size ranged between 30 and 38%. Our infarct size results in the control group are virtually identical to those of Tekin et al…”

Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

“…Integrated release of lactate dehydrogenase during reperfusion, a marker of ischemic injury [36], was measured as previously published in the literature.…”

Heat stress upregulates chaperone heat shock protein 70 and antioxidant manganese superoxide dismutase through reactive oxygen species (ROS), p38MAPK, and Akt

“…It has been reported that heat stress produced moderate upregulation of MnSOD in cardiac myocytes conferring protection against hypoxia-reoxygenation injury (Yamashita et al 1997). On the contrary, lack of increase in MnSOD activity in rat heart after hyperthermia has also been reported (Tekin et al 2001). Thermal injury of the skin over a long period of time has been associated with development of cancerous lesions (Aziz et al 1998).…”