摘要
目的 研究 p38丝裂原激活蛋白激酶 (MAPK)选择性抑制剂SB2 0 35 80对乳鼠小脑颗粒神经元凋亡的保护作用。方法 SD乳鼠小脑颗粒神经元培养 ,琼脂糖凝胶电泳 ,SAPK/JNK分析试剂盒作激酶分析。结果 PI 3 K的特异性抑制剂LY2 940 0 2诱导小脑颗粒神经元凋亡 ,但SB2 0 35 80通过抑制细胞凋亡而促进小脑颗粒神经元的存活 ,且有浓度依赖性。LY2 940 0 2诱导凋亡的颗粒神经元中c Jun的表达量和磷酸化水平均升高 ,JNK被激活。但是 ,当小脑颗粒神经元生长在含SB2 0 35 80的高钾培养基中 ,c Jun的表达量、磷酸化水平和JNK的活性都明显的降低。结论 SB2 0 35 80通过抑制JNK的活性 ,降低c Jun的表达和磷酸化水平 。
AIM To study the effect of the specific p38 MAPK inhibitor SB203580 on apoptosis induced by PI 3 K inhibitor LY294002 and its mechanisms in cerebellar granule neurons.METHODS Cerebellar granule neurons culture, agar gel eletrophoresis, and SAPK/JNK assay kit were used to measure SAPK/JNK activity. RESULTS Cultured cerebellar granule neurons died by apoptosis in a concentration dependent manner when treated with LY294002, a specific inhibitor of PI 3 K. But the specific p38 MAPK inhibitor SB203580 promoted the survival of cerebellar granule neurons by blocking apoptosis. This protective action was shown to be in a concentration dependent manner. The expression and phosphorylation of c Jun increased, and the activity of c Jun N terminal protein kinase (JNK) was elevated when cerebellar granule neurons were cultured with LY294002 50 μmmol·L -1 in cHK medium. But when the cerebellar granule neurons treated with LY294002 50 μmmol·L -1 were exposed to SB203580 25 μmmol·L -1 , the expression and phosphorylation of c Jun, and the activity of JNK all decreased evidently. CONCLUSION SB203580 inhibited the activation of JNK and decreased the expression and phosphorylation of c Jun to protect granule neurons from apoptosis induced by LY294002.
出处
《药学学报》
CAS
CSCD
北大核心
2000年第7期496-499,共4页
Acta Pharmaceutica Sinica
基金
国家自然科学基金!(39770851
39870265)
广东省自然科学基金!(970094
970278)
国家杰出青年科学基金!(39625022)共同资助项目
