Overexpression of HSPA12B Protects Against Cerebral Ischemia/Reperfusion Injury via a PI3K/Akt-Dependent Mechanism
Document Type
Article
Publication Date
1-1-2013
Description
Background and purpose: HSPA12B is a newly discovered member of the Hsp70 family proteins. This study investigated the effects of HSPA12B on focal cerebral ischemia/reperfusion (I/R) injury in mice. Methods: Transgenic mice overexpressing human HSPA12B (Tg) and wild-type littermates (WT) were subjected to 60. min of middle cerebral artery occlusion to induce ischemia and followed by reperfusion (I/R). Neurological deficits, infarct volumes and neuronal death were examined at 6 and 24. hrs after reperfusion. Blood-brain-barrier (BBB) integrity and activated cellular signaling were examined at 3. hrs after reperfusion. Results: After cerebral I/R, Tg mice exhibited improvement in neurological deficits and decrease in infarct volumes, when compared with WT I/R mice. BBB integrity was significantly preserved in Tg mice following cerebral I/R. Tg mice also showed significant decreases in cell injury and apoptosis in the ischemic hemispheres. We observed that overexpression of HSPA12B activated PI3K/Akt signaling and suppressed JNK and p38 activation following cerebral I/R. Importantly, pharmacological inhibition of PI3K/Akt signaling abrogated the protection against cerebral I/R injury in Tg mice. Conclusions: The results demonstrate that HSPA12B protects the brains from focal cerebral I/R injury. The protective effect of HSPA12B is mediated though a PI3K/Akt-dependent mechanism. Our results suggest that HSPA12B may have a therapeutic potential against ischemic stroke.
Citation Information
Ma, Yujie; Lu, Chen; Li, Chuanfu; Li, Rongrong; Zhang, Yangyang; Ma, He; Zhang, Xiaojin; Ding, Zhengnian; and Liu, Li. 2013. Overexpression of HSPA12B Protects Against Cerebral Ischemia/Reperfusion Injury via a PI3K/Akt-Dependent Mechanism. Biochimica et Biophysica Acta - Molecular Basis of Disease. Vol.1832(1). 57-66. https://doi.org/10.1016/j.bbadis.2012.10.003 PMID: 23046810 ISSN: 0925-4439