Extracellular signal-regulated kinase involved in NGF/VEGF-induced neuroprotective effect.
Compelling evidence has shown that extracellular signal-regulated kinase (ERK) is widely expressed in many tissues, including the brain. In the present work, we investigated the temporospatial alterations of ERK1 immunoreactivity in hippocampus and perifocal cortex, and the expression involved in NGF/VEGF-induced neuroprotective effect. We demonstrated that ERK1 expression was first increased in hippocampal CA3/DG 1 h after reperfusion, then it was also increased 6 h after reperfusion in other brain regions, with a peak at day 1-3, and then gradually decreased to basal level at day 14. The expression of caspase-3 was strongly increased 1 h after reperfusion, with peak demonstrated at 3d. NGF/VEGF significantly inhibited the expression of ERK1 and caspase-3. These results suggest that ERK1 signaling pathway may be involved in neuronal cell death and NGF/VEGF-induced neuroprotective effect and there appeared an association between ERK and caspase-3. Inhibition of the ERK signaling pathway might therefore provide an efficient way to prevent neuronal cell death after ischemic cerebral injuries.
Yang
Ji-Ping
JP
Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305# East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
Liu
Xin-Feng
XF
Liu
Huai-Jun
HJ
Xu
Ge-Lin
GL
Ma
Yu-Ping
YP
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*
D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3