Sun Ming, Zhao Yumei, Xu Chao
Department of Neurochemistry, Beijing Neurosurgical Institute, 6 Tiantan Xi Li, Chongwen District, 100050, Beijing, China.
Cell Mol Neurobiol. 2008 Jan;28(1):71-85. doi: 10.1007/s10571-007-9250-1. Epub 2007 Dec 21.
Some data have shown the functional connection between calpain and caspase-3. Here, we investigated the cross-talk between calpain and caspase-3 in penumbra and core during focal cerebral ischemia-reperfusion.
The activities of calpain and the levels of calpastatin, microtubule-associated protein-2 (MAP-2), and spectrin in penumbra and core at 3 or 23 h of reperfusion (R 3 h or R 23 h) after 1-h focal cerebral ischemia in rats were determined in sham- or caspase-3 inhibitor z-DEVD-CHO-treated rats.On the other hand, the determination of the activities of caspase-3 and the levels of MAP-2 and spectrin was done in sham- or calpain-inhibitor I-treated rats.
z-DEVD-CHO (600 ng/rat, i.c.v.) markedly reduced the mu- and m-calpain activities in penumbra and the m-calpain activities in core at R 3 h and R 23 h, and enhanced the calpastatin levels in penumbra at R 3 h and in core at R 3 h and R 23 h significantly; however, it had no significant effects on the mu-calpain activities in core and the calpastatin levels in penumbra at R 23 h. Calpain inhibitor I (0.8 mg/rat, i.c.v.) markedly reduced the caspase-3 activities in core at R 3 h and R 23 h, but not in penumbra. Both calpain and caspase-3 inhibitors increased the levels of MAP-2 and spectrin in penumbra and core significantly after focal cerebral ischemia-reperfusion.
Our data provide direct evidence to demonstrate the cross-talk between calpain and caspase-3 in penumbra and core during focal cerebral ischemia-reperfusion.
一些数据显示了钙蛋白酶与半胱天冬酶 - 3之间的功能联系。在此，我们研究了局灶性脑缺血再灌注期间半暗带和梗死核心区中钙蛋白酶与半胱天冬酶 - 3之间的相互作用。
在假手术组或经半胱天冬酶 - 3抑制剂z - DEVD - CHO处理的大鼠中，测定大鼠局灶性脑缺血1小时后再灌注3小时（R 3 h）或23小时（R 23 h）时半暗带和梗死核心区中钙蛋白酶的活性、钙蛋白酶抑制蛋白、微管相关蛋白 - 2（MAP - 2）和血影蛋白的水平。另一方面，在假手术组或经钙蛋白酶抑制剂I处理的大鼠中，测定半胱天冬酶 - 3的活性、MAP - 2和血影蛋白的水平。
z - DEVD - CHO（600 ng/大鼠，脑室内注射）显著降低了R 3 h和R 23 h时半暗带中μ - 钙蛋白酶和m - 钙蛋白酶的活性以及梗死核心区中m - 钙蛋白酶的活性，并显著提高了R 3 h时半暗带以及R 3 h和R 23 h时梗死核心区中钙蛋白酶抑制蛋白的水平；然而，它对R 23 h时梗死核心区中μ - 钙蛋白酶的活性和半暗带中钙蛋白酶抑制蛋白的水平没有显著影响。钙蛋白酶抑制剂I（0.8 mg/大鼠，脑室内注射）显著降低了R 3 h和R 23 h时梗死核心区中半胱天冬酶 - 3的活性，但对半暗带中没有影响。在局灶性脑缺血再灌注后，钙蛋白酶抑制剂和半胱天冬酶 - 3抑制剂均显著提高了半暗带和梗死核心区中MAP - 2和血影蛋白的水平。
我们的数据提供了直接证据，证明局灶性脑缺血再灌注期间半暗带和梗死核心区中钙蛋白酶与半胱天冬酶 - 3之间存在相互作用。
