Neuroprotection against ischemic brain injury by knockdown of hematopietic progenitor kinase 1 expression.

Abstract

In this study, we investigated the role of hematopietic progenitor kinase 1 (HPK1) in delayed neuronal damage after cerebral ischemia and the possible regulatory mechanisms of this event. Our data show that tyrosine phosphorylation of HPK1 was significantly increased at 6 h of ischemic-reperfusion compared with sham control. The increase in p-HPK1, p-MLK3, p-MKK7, and p-JNK3 was attenuated by HPK1 antisense oligodeoxynucleotides intra-cerebroventricular infusion, but not MS-ODNs or vehicle. Intracerebroventricular infusion of antisense oligodeoxynucleotides also increased the number of surviving pyramidal neurons, whereas MS-ODNs or vehicle (TE) groups had no effects. These results indicate that knockdown of HPK1 expression provides neuroprotection through downregulation activation of the MLK3-MKK7-JNK3 pathway following cerebral ischemia in the rat hippocampus CA1 subfield.

• Authors: Ting Li, Dong Han, Juan Chen, Xiu-Ju Yu, Guang-Yi Zhang
• Journal: Neuroreport (Neuroreport) Vol. 19 Issue 6 Pg. 647-51 (Apr 16 2008) ISSN: 0959-4965 [Print] England
• PMID: 18382279 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oligodeoxyribonucleotides, Antisense
• Mitogen-Activated Protein Kinase 10
• hematopoietic progenitor kinase 1
• Protein Serine-Threonine Kinases
• MAP Kinase Kinase Kinases
• MAP Kinase Kinase 7

Topics

• Animals
• Blotting, Western
• Brain (metabolism)
• Enzyme Activation (physiology)
• Hypoxia-Ischemia, Brain (metabolism)
• Immunoprecipitation
• MAP Kinase Kinase 7 (metabolism)
• MAP Kinase Kinase Kinases (metabolism)
• Male
• Mitogen-Activated Protein Kinase 10 (metabolism)
• Nerve Degeneration (metabolism)
• Oligodeoxyribonucleotides, Antisense
• Phosphorylation
• Protein Serine-Threonine Kinases (antagonists & inhibitors, genetics)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (physiology)
• Mitogen-Activated Protein Kinase Kinase Kinase 11