Overexpression of HSPA12B protects against cerebral ischemia/reperfusion injury via a PI3K/Akt-dependent mechanism

被引：72

作者：

Ma, Yujie ^{[1
]}

Lu, Chen ^{[1
,2
]}

Li, Chuanfu ^{[2
]}

Li, Rongrong ^{[3
]}

Zhang, Yangyang ^{[1
]}

Ma, He ^{[3
]}

Zhang, Xiaojin ^{[1
]}

Ding, Zhengnian ^{[3
]}

Liu, Li ^{[1
]}

机构：

[1] Nanjing Med Univ, Dept Geriatr, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China

[2] E Tennessee State Univ, Dept Surg, Johnson City, TN 37614 USA

[3] Nanjing Med Univ, Dept Anesthesiol, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2013年 / 1832卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Cerebral ischemia/reperfusion; Heat shock protein A12B (HSPA12B); PI3K/Alct signaling; Apoptosis; Neuroprotective agent; CELL-DEATH; CARDIAC DYSFUNCTION; GENE PROTECTS; ISCHEMIA; BRAIN; ACTIVATION; EXPRESSION; MICE; NEUROPROTECTION; RESISTANCE;

D O I：

10.1016/j.bbadis.2012.10.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 (UR) injury in mice. Methods: Transgenic mice overexpressing human HSPA12B (Tg) and wild-type littermates (WT) were subjected to 60 mm 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. Importantly, pharmacological inhibition of PI3K/Alct 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. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：57 / 66

页数：10

共 39 条

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AN ANG1-TIE2-PI3K AXIS IN NEURAL PROGENITOR CELLS INITIATES SURVIVAL RESPONSES AGAINST OXYGEN AND GLUCOSE DEPRIVATION [J].