Heat shock protein 72 inhibits c-Jun N-terminal kinase 3 signaling pathway via Akt1 during cerebral ischemia

J Neurol Sci. 2012 Jun 15;317(1-2):123-9. doi: 10.1016/j.jns.2012.02.011. Epub 2012 Mar 3.


Although recent researches show that Heat Shock Protein 72 (HSP72) plays an important role in neuronal survival, little knowledge is known about the precise mechanisms during cerebral ischemia/reperfusion (I/R). Our present study investigated the neuroprotective mechanisms of HSP72 against ischemic brain injury induced by cerebral I/R. Mild heat shock pretreatment was employed to induce the overexpression of HSP72 by immersing rats into the water bath at 42°C for 20 min before cerebral I/R. HSP72 antisense oligodeoxynucleotides (ODNs) were used to inhibit HSP72 expression by intracerebroventricular infusion once per day for 3 days before cerebral I/R animal model was induced by four-vessel occlusion for 15 min transient ischemia and then reperfused for various time in Sprague-Dawley rats. Immunoprecipitation and immunoblotting were used to detect the expression of the related proteins. HE-staining and TUNEL-staining were carried out to examine the neuronal death of hippocampal CA1 region. Results showed that mild heat shock could increase the phosphorylation of protein kinase B (Akt), inhibit the assembly of MLK3-MKK7-JNK3 signaling module, diminish the phosphorylation of JNK3 and c-Jun, and decrease the activation of caspase-3. Furthermore, mild heat shock could significantly protect neurons against cerebral I/R. Whereas, all of the aforementioned effects of mild heat shock were reversed by HSP72 antisense ODNs. In summary, our results imply that Akt1 activation is involved in the neuroprotection of HSP72 against ischemic brain injury via suppressing JNK3 signaling pathway and provide a new experimental foundation for stroke therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / metabolism*
  • Brain Ischemia / prevention & control
  • HSP72 Heat-Shock Proteins / biosynthesis
  • HSP72 Heat-Shock Proteins / physiology*
  • Infusions, Intraventricular
  • MAP Kinase Signaling System / genetics*
  • Male
  • Mitogen-Activated Protein Kinase 10 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 10 / physiology*
  • Oligonucleotides, Antisense / administration & dosage
  • Proto-Oncogene Proteins c-akt / physiology*
  • Rats
  • Rats, Sprague-Dawley


  • HSP72 Heat-Shock Proteins
  • Oligonucleotides, Antisense
  • Mitogen-Activated Protein Kinase 10
  • Akt1 protein, rat
  • Proto-Oncogene Proteins c-akt