title: Overexpression of HSPA12B protects against cerebral ischemia/reperfusion injury via a PI3K/Akt-dependent mechanism.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Geriatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Ma
authors.forename: Chen
authors.initials: C
authors.lastname: Lu
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.forename: Rongrong
authors.initials: R
authors.lastname: Li
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Ma
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhengnian
authors.initials: Z
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D018840:HSP70 Heat-Shock Proteins; C472131:HSPA12B protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt