Neuroprotection against ischemic brain injury by knockdown of hematopietic progenitor kinase 1 expression.
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.
Li
Ting
T
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Han
Dong
D
Chen
Juan
J
Yu
Xiu-Ju
XJ
Zhang
Guang-Yi
GY
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D047468:Immunoprecipitation; D048688:MAP Kinase Kinase 7 / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008297:Male; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
D048688:MAP Kinase Kinase 7; D020930:MAP Kinase Kinase Kinases; D048057:Mitogen-Activated Protein Kinase 10; D020319:Oligodeoxyribonucleotides, Antisense; D017346:Protein Serine-Threonine Kinases; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; C102102:hematopoietic progenitor kinase 1