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 24hrs 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.
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 humanHSPA12B (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 24hrs 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.
Authors: Vaithinathan Selvaraju; Sumanth C Suresh; Mahesh Thirunavukkarasu; Jayakanthan Mannu; Jocelyn L C Foye; Premendu P Mathur; J Alexander Palesty; Juan A Sanchez; David W McFadden; Nilanjana Maulik Journal: J Cardiovasc Transl Res Date: 2017-03-09 Impact factor: 4.132
Authors: Jinzi Wu; Rongrong Li; Wenjun Li; Ming Ren; Nopporn Thangthaeng; Nathalie Sumien; Ran Liu; Shaohua Yang; James W Simpkins; Michael J Forster; Liang-Jun Yan Journal: Free Radic Biol Med Date: 2017-10-07 Impact factor: 7.376