Ceramide from sphingomyelin hydrolysis differentially mediates mitogen-activated protein kinases (MAPKs) activation following cerebral ischemia in rat hippocampal CA1 subregion.
Ceramide from sphingomyelin hydrolysis differentially mediates mitogen-activated protein kinases (MAPKs) activation following cerebral ischemia in rat hippocampal CA1 subregion.
复制标题
来自鞘磷脂水解的神经酰胺差异地介导了大鼠海马CA1亚区域脑缺血后的有丝分裂原激活的蛋白激酶（MAPK）激活。
DOI：
10.1016/s1674-8301(10)60021-8
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发表时间：
2010-03
影响因子：
2.3
通讯作者：
Guo, Jun
中科院分区：
文献类型：
--
作者：
Sun, Xian;Liu, Chao;Qian, Min;Zhao, Zhenghong;Guo, Jun
目的：探讨神经酰胺在脑缺血再灌流中丝裂原活化蛋白激酶(MAPKs)活化中的作用。采用四血管结扎法(4-VO)复制大鼠脑缺血模型。在诱导大鼠脑缺血前，在大鼠海马区CA1区注射鞘磷脂酶抑制剂TPCK。免疫印迹法检测细胞外信号调节蛋白激酶(ERK)和c-jun氨基末端蛋白激酶(JNK)的活性。缺血再灌注1h，JNK活性达到峰值，ERK急剧失活(P<；0.05)。神经鞘磷脂酶抑制剂显著降低了JNK的二磷酸化水平，但明显逆转了ERK的急剧失活(P<；0.05)。神经酰胺信号通路在脑缺血时通过神经鞘蛋白水解酶上调，促进JNK激活，抑制ERK激活，最终导致脑缺血损伤。
To explore the role that ceramide plays in the activation of mitogen-activated protein kinases (MAPKs) during cerebral ischemia and reperfusion. Rats were subjected to ischemia by the four-vessel occlusion (4-VO) method. The sphingomyelinase inhibitor TPCK was administered to the CA1 subregion of the rat hippocampus before inducing ischemia. Western blot was used to examine the activity of extracellular-signal regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) using antibodies against ERK, JNK and diphosphorylated ERK and JNK. At 1h reperfusion post-ischemia, JNK reached its peak activity while ERK was undergoing a sharp inactivation (P < 0.05). The level of diphosphorylated JNK was significantly reduced but the sharp inactivation of ERK was visibly reversed (P < 0.05) by the sphingomyelinase inhibitor. The ceramide signaling pathway is up-regulated through sphingomyelin hydrolysis in brain ischemia, promoting JNK activation and suppressing ERK activation, culminating in the ischemic lesion.