The role of heat shock proteins (Hsp70 and Hsp27) in protection against ischemic injury in the myocardium and cerebral cortex.

摘要

Ischemic injury induces expression of heat shock proteins (Hsp70 and Hsp27). After ischemia and reperfusion, mRNA for Hsp70 progressively accumulated in the ischemic area of isolated and perfused hearts but not in the necrotic area of the ischemic zone, suggesting that Hsp70 expression in the area at risk may play a role in myocardial recovery after ischemia. The protective role of Hsp70 was examined in transgenic mice over-expressing the human Hsp70. After ischemia, upon reperfusion, transgenic hearts compared to non-transgenic hearts had significantly improved recovery of contractile force and showed less cellular injury. These results demonstrate that constitutive expression of the human Hsp70 protects the mouse myocardium from ischemic injury. In the brain, no significant difference in infarct areas was observed between transgenic and non-transgenic mice following 24 hour-occlusion of the middle cerebral artery. However, non-transgenic mice showed ipsilateral hippocampal injury while no injury was detected in the hippocampus of transgenic mice. This suggests that Hsp70 did not protect against severe ischemic injury induced in the cerebral cortex but protected hippocampal neurons from injury.; While Hsp27 was constitutively expressed in select populations of brain stem and spinal cord neurons of the adult rat, Hsp27 was not present in the cerebral cortex. However, focal cortical ischemia induced Hsp27 in most astrocytes of the ipsilateral cerebral cortex. Different distributions of Hsp27 and Hsp70 suggested that Hsp70 was expressed in the penumbra and that ischemic injury induced changes in gene expression that vary according to cell type and brain region. Cortical spreading depression triggered by cortical application of potassium chloride induced Hsp27 in GFAP-positive astrocytes of the ipsilateral cortex. Blockade of spreading depression by systemic administration of MK-801 significantly reduced Hsp27 expression in the parietal cortex. These results suggest that spreading depression can trigger Hsp27 astrocytic expression. It may be that Hsp27 plays a role in spreading depression-induced ischemic tolerance in neurons through protection of astrocyte functions.