An Inhibitor of p38 MAPK Prevents Apoptosis of Cultured Cerebellar Granule Neurons via Inhibiting the Activity of JNK
- VernacularTitle:p38 MAPK抑制剂通过抑制JNK活性抑制培养的小脑颗粒神经元凋亡
- Author:
Mingtao LI
;
Wenya WANG
;
Juan SUN
;
Xiaoli TANG
;
Xingwen SU
;
Pengxin QIU
;
Guangmei YAN
- Publication Type:Journal Article
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2001;22(3):165-169
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】To study the effect of the specific p38 mitogen-activated protein kinase(p38 MAPK) inhibitor SB203580 on apoptosis of cerebellar granule neurons induced by low potassium.【Methods】Apoptosis was induced by switching the cultured cerebellar granule neurons from a culture medium containing K+ 25 mmol*L-1 to a medium containing K+ 5 mmol*L-1 (cLK).Fragmentation of DNA was analyzed using agarose gel eletrophoresis.SAPK/JNK activity was measured by SAPK/JNK assay kit.【Results】Low potassium resulted in apoptosis as characterized by morphological and biochemical features,but the specific p38 MAPK inhibitor SB203580 improved the survival of cerebellar granule neurons cultured in cLK medium by blocking apoptosis in a concentration-dependent manner.The expression and phosphorylation of c-Jun increased and the activity of c-Jun N-terminal protein kinase (JNK) elevated when cerebellar granule neurons were cultured in cLK medium.But when the cerebellar granule neurons cultured in cLK medium were exposed to 25 μmol*L-1 SB203580,the expression and phosphorylation of c-Jun and the activity of JNK were both decreased evidently.【Conclusions】These results indicate that SB203580 inhibits the activation of JNK and phosphorylation of c-Jun,and therefore protects granule neurons from apoptosis induced by low potassium.