摘要
【目的】研究特异性p38分裂原激活的蛋白激酶 (MAPK)抑制剂SB2 0 35 80对低钾诱导的小脑颗粒神经元凋亡的作用。【方法】把体外培养的小脑颗粒神经元从含去极化浓度钾离子 (KCl 2 5mmol·L-1)的培养基中转移至低钾培养基 (KCl5mmol·L-1)中诱导神经元凋亡。凝胶电泳分析DNA片段 ,SAPK/JNK分析盒测定c JunN 末端蛋白激酶 (JNK)活性。【结果】低钾诱导小脑颗粒神经元的具有典型形态学和生化特征的凋亡。特异性的p38MAPK抑制剂SB2 0 35 80通过抑制细胞凋亡 ,促进低钾环境中培养的小脑颗粒神经元存活。这种保护作用具有浓度依赖性。培养于低钾环境中的颗粒神经元 ,c Jun表达和磷酸化水平升高了 ,且激活了JNK活性。当小脑颗粒神经元生长在含SB2 0 35 80 2 5 μmol·L-1的低钾培养基中 ,c Jun表达、磷酸化水平和JNK活性都明显降低。【结论】SB2 0 35 80抑制JNK活性 ,降低c
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. 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. 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.
出处
《中山医科大学学报》
CSCD
北大核心
2001年第3期165-169,F003,共6页
Academic Journal of Sun Yat-sen University of Medical Sciences
基金
ThegrantfromtheNationalFoundationofOutstandingYoungScientistsofChina( 396 2 5 0 2 2 )
theNationalNaturalScienceFoundationofChina ( 39870 2 6 5and 3980 0 16 2 )
