摘要
目的：研究特异性c-Jun氨基末端激酶(JNK)抑制剂SP600125对低钾诱导的小脑颗粒神经凋亡的保护作用。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 25 mmol／L)的培养基中转移至低钾培养基(KCl 5mmol／L)中诱导神经元凋亡。以Western blot法检测JNK和c-Jtm的磷酸化水平。结果：低钾(KCl 5mmol／L)磷酸化并激活JNK，诱导c-Jun磷酸化和小脑颗粒经济元凋亡。SP600125通过抑制c-Jun磷酸化而浓度依赖性地促进低钾环境中培养的小脑颗粒神经元的存活。其保护作用的半数有效量(ED50)为1．01μmol／L。结论：SP600125通过特异性地抑制JNK活性而对低钾培养的小脑颗粒神经元具有保护作用；提示JNK是介导低钾诱导的小脑颗粒神经元凋亡的关键激酶，它可能可以作为干扰神经元凋亡的药物的作用靶点。
To study the effect of the specific p38 MAPK inhibitor SB203580 on apoptosis induced by low potassium and its mechanisms by using agarose gel eletrophoresis and SAPK/JNK assay kit to measure SAPK/JNK activity. The results showed that switching cerebellar granule neurons from depolarizing conditions (KCl 25 mmol/L) to non depolarizing conditions (KCl 5 mmol/L,cLK) exhibited the morphological and biochemical features characteristic of apoptosis. But the specific p38 MAPK inhibitor SB203580 promoted the survival of cerebellar granule neurons cultured in cLK medium by blocking apoptosis. This protective action was in a concentration dependent manner. The expression and phosphorylation of c Jun increased, 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 SB203585 25 μmol/L, the expression and phosphorylation of c Jun and the activity of JNK all decreased evidently.It indicated that SB203580 inhibited the activation of JNK and decreased the phosphorylation of c Jun to protect granule neurons from apoptosis induced by low potassium.
出处
《第一军医大学分校学报》
2004年第2期190-190,共1页
Journal of Branch Campus of the First Military Medical University
基金
广东省自然科学基金!No.970278
No.970094
国家自然科学基金!No.39770 851
No39870265
国家杰出青年科学基金!No.39625022
