Gu Z, Jiang Q, Zhang G
Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, PR China.
Neuroreport. 2001 Nov 16;12(16):3487-91. doi: 10.1097/00001756-200111160-00023.
The alterations and involvement of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) activation were examined in the hippocampal CA1 region in a rat model of global brain ischemic tolerance. Western blotting study showed that ERK activation (diphosphorylation) level was decreased (3.75-, 0.56-, and 0.23-fold vs sham control) and JNK activation level was increased (3.82-, 4.63-, and 5.30-fold vs sham control) 3 days after more severe ischemic insults (6 min, 8 min, and 10 min of ischemia, respectively). These alterations were significantly prevented by pretreatment with preconditioning ischemia, which also provided neuronal protection against ischemic injury. Inhibition of ERK activation after preconditioning ischemia by PD98059, a specific ERK kinase inhibitor, significantly prevented the inhibitory effects of preconditioning ischemia on both JNK activation and ischemic injury. The results suggest that ERK activation after preconditioning ischemia may result in the prevention of JNK activation and thus be involved in the protective responses in ischemic tolerance in hippocampal CA1 region.
在全脑缺血耐受大鼠模型中，检测了细胞外信号调节激酶（ERK）和c-Jun氨基末端蛋白激酶（JNK）激活的改变及参与情况。蛋白质印迹研究表明，在更严重的缺血性损伤（分别为6分钟、8分钟和10分钟缺血）3天后，ERK激活（双磷酸化）水平降低（与假手术对照组相比分别为3.75倍、0.56倍和0.23倍），而JNK激活水平升高（与假手术对照组相比分别为3.82倍、4.63倍和5.30倍）。预处理缺血可显著预防这些改变，其还能为神经元提供针对缺血性损伤的保护作用。用特异性ERK激酶抑制剂PD98059抑制预处理缺血后的ERK激活，可显著预防预处理缺血对JNK激活和缺血性损伤的抑制作用。结果表明，预处理缺血后的ERK激活可能导致JNK激活受到抑制，从而参与海马CA1区缺血耐受中的保护反应。
