JNK and p38 were involved in hypoxia and reoxygenation-induced apoptosis of cultured rat cerebellar granule neurons.
As a model of the reperfusion injury found in stroke, we treated cerebellar granule neurons (CGNs) with hypoxia followed by reoxygenation. Hypoxia for 3h followed by 24h reoxygenation (H/R) induced a typical apoptosis of CGNs. CGNs exposed to H/R responded by activating JNK, increasing the expression of p38 and ultimately caused CGNs dying. Furthermore, apoptosis of CGNs induced by H/R was inhibited by pre-treatment with SB203580 or SP600125, and the inhibitory effect of SB203580 was greater than that of SP600125. Additionally, we also found that H/R temporally activated Akt and inactivated glycogen synthesis kinase-3beta (GSK-3beta), two proteins the functions of which were important in cell survival and energy metabolism. These findings demonstrated that H/R-induced apoptosis in CGNs by enhancing JNK and p38 activity, which contributed at least in part to H/R-induced apoptosis of CGNs.
Liu
Ai-Ling
AL
Department of Pharmacology, Sun Yat-Sen Medical School, Sun Yat-Sen University, Guangdong, China.
Wang
Xin-Wei
XW
Liu
Ai-Hua
AH
Su
Xing-Wen
XW
Jiang
Wei-Jian
WJ
Qiu
Peng-Xin
PX
Yan
Guang-Mei
GM
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D002843:Chromatin / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*
D002843:Chromatin; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010100:Oxygen