Ischemic postconditioning protects brain from ischemia/reperfusion injury by attenuating endoplasmic reticulum stress-induced apoptosis through PI3K-Akt pathway.

Endoplasmic reticulum (ER) stress has been implicated in the pathology of cerebral ischemia. During prolonged period of stress or when the adaptive response fails, apoptotic cell death ensues. Cerebral ischemic postconditioning (Postcond) has been shown to reduce cerebral ischemia/reperfusion (I/R) injury in both focal and global cerebral ischemia model. However, the mechanism remains to be understood. This study aimed to elucidate whether Postcond attenuates brain I/R damage by suppressing ER stress-induced apoptosis and if the phosphatidylinositol-3kinase/Akt (PI3K/Akt) pathway is involved. A focal cerebral ischemia rat model was used in the study. Rat brain infarct size and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in ischemic penumbra were assessed after reperfusion of the brain. The expressions of C/EBP-homologous protein (CHOP), caspase-12, glucose-regulated protein 78 (GRP78) and the phosphorylation of Akt (Ser473) in ischemic penumbra were measured after reperfusion. Our results showed that Postcond significantly attenuated brain I/R injury, as shown by reduction in infarct size, cell apoptosis, CHOP expression, caspase-12 activation and increase in GRP78 expression. LY294002, a phosphoinositide 3-kinase inhibitor, increased the number of TUNEL-positive cells suppressed by Postcond in penumbra. In addition, LY294002 diminished the effect of Postcond on the activation of CHOP, caspase-12 and GRP78. These results suggest that Postcond protects brain from I/R injury by suppressing ER stress-induced apoptosis and PI3K/Akt pathway is involved.

Yuan Y ，Guo Q ，Ye Z ，Pingping X ，Wang N ，Song Z ... -  《-》

Nerve growth factor protects the ischemic heart via attenuation of the endoplasmic reticulum stress induced apoptosis by activation of phosphatidylinositol 3-kinase.

Wei K ，Liu L ，Xie F ，Hao X ，Luo J ，Min S ... -  《International Journal of Medical Sciences》

Remote ischemic postconditioning protects the brain from global cerebral ischemia/reperfusion injury by up-regulating endothelial nitric oxide synthase through the PI3K/Akt pathway.

Remote ischemic postconditioning (RIPoC) attenuates ischemia/reperfusion (I/R) injury in the heart, lung and hind limb. RIPoC performed in the hind limb reduces brain injury following focal cerebral ischemia in rats. Whether RIPoC has a neuroprotective effect with respect to global cerebral I/R injury is, however, unknown, and the mechanism of neuroprotection needs further elucidation. Here we investigated whether RIPoC could reduce global cerebral I/R injury in rats and whether this neuroprotective effect was induced by up-regulating endothelial nitric oxide synthase (eNOS) through the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway. Global cerebral ischemia was performed via 8min of four-vessel occlusion. Neuronal density, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and expression of Bcl-2 and Bax in the hippocampal CA1 region were assessed after reperfusion. Morris water maze task was used to quantify spatial learning and memory deficits after reperfusion. The expression of eNOS, phosphorylated eNOS (Ser1177), Akt and phosphorylated Akt (Ser473) in the CA1 region was measured after reperfusion. RIPoC significantly attenuated delayed neuronal death and reduced the spatial learning and memory deficits associated with global cerebral ischemia. Pre-administration of N(ω)-nitro-l-arginine methyl ester (a nonselective NOS inhibitor) significantly abolished the neuroprotective effect of RIPoC. Moreover, pre-administration of LY294002 (a highly selective inhibitor of PI3K) not only significantly reversed the neuroprotective effect of RIPoC, but also obviously inhibited the up-regulation of eNOS induced by RIPoC. Our findings suggest that RIPoC protects the brain against global cerebral I/R injury and that this neuroprotection is mediated by up-regulating eNOS through the PI3K/Akt pathway.

Peng B ，Guo QL ，He ZJ ，Ye Z ，Yuan YJ ，Wang N ，Zhou J ... -  《-》

Erythropoietin protects against cisplatin-induced nephrotoxicity by attenuating endoplasmic reticulum stress-induced apoptosis.

Kong D ，Zhuo L ，Gao C ，Shi S ，Wang N ，Huang Z ，Li W ，Hao L ... -  《-》

Hypothermia protects the brain from transient global ischemia/reperfusion by attenuating endoplasmic reticulum response-induced apoptosis through CHOP.

Liu X ，Wang M ，Chen H ，Guo Y ，Ma F ，Shi F ，Bi Y ，Li Y ... -  《PLoS One》