These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: [Effects of caspase-3 inhibitor on the neuronal apoptosis in rat cerebral cortex after ischemia-reperfusion injury].
    Author: Yu SZ, Yan L, Wang Q, An TL, Guan XQ.
    Journal: Zhonghua Bing Li Xue Za Zhi; 2006 Mar; 35(3):165-70. PubMed ID: 16630506.
    Abstract:
    OBJECTIVE: To investigate the effect of z-DEVD-fmk, a caspase-3 inhibitor on the neuronal apoptosis in ischemia-reperfusion region (IRR) of rat cerebral cortex. METHODS: Rats prepared by middle cerebral artery occlusion and reperfusion were used as the research model. The animals were divided into A group (untreated), B group (DMSO control) and C group (treated with z-DEVD-fmk). Before reperfusion, z-DEVD-fmk (7 microg/kg) was injected into the ischemic side of ventriculus cerebri of C group rats. The expression and activation of caspase-3, expression and cleavage of poly (ADP-ribose) polymerase (PARP), and apoptotic neurons in the temporal-parietal cortex IRRs (SPAB method) of all the rats were studied using Western blotting, in situ apoptotic detection (TUNEL method) and immunohistochemistry. RESULTS: In the cerebral IRRs of A, B, C groups reperfused for 1 h and 24 h, the quantities of caspase-3 precursor were 16.7 +/- 3.0, 11.5 +/- 3.0 and 47.5 +/- 3.5, and 76.1 +/- 3.5, 71.3 +/- 6.4 and 88.2 +/- 5.5, respectively; the caspase-3 fragments (12,000) 8.2 +/- 2.3, 9.4 +/- 1.2 and 4.3 +/- 1.6, and 59.0 +/- 6.3, 60.5 +/- 7.2 and 17.3 +/- 2.8, respectively; the PARP 12.6 +/- 3.0, 13.9 +/- 2.0 and 53.7 +/- 4.1, and 67.5 +/- 8.6, 61.1 +/- 6.6 and 93.6 +/- 4.1, respectively; the PARP fragments (24,000) 6.0 +/- 0.7, 6.6 +/- 1.2, 3.6 +/- 1.1, and 27.4 +/- 2.6, 25.8 +/- 3.2, 12.1 +/- 2.8 (relative quantity, x+/- s); the densities of apoptotic neurons 83.3 +/- 7.5, 84.3 +/- 5.7 and 45.7 +/- 4.0, and 197.4 +/- 11.8, 185.2 +/- 11.2 and 99.1 +/- 5.8 (cell number/0.1 mm(2), x+/- s). These results showed that in the cerebral IRRs of both A and B groups, all caspase-3 expression and activation, PARP expression and cleavage, and neuronal apoptosis were increased relevantly along with prolongation of the reperfusion time (P < 0.05 - 0.001). At each time point of the reperfusion, caspase-3 activation, PARP cleavage and neuronal apoptosis in the cerebral IRR of C group were significantly less than those of the former two groups (P < 0.05 - 0.001). The variations of the 5 parameters of A, B and C groups correlated positively with one another (r = 0.630 - 0.942, P < 0.01). The cells expressing PARP were mainly neurons in the cerebral IRRs of all the animals, but the difference of their number was not distinct among the 3 groups. CONCLUSIONS: It is an important mechanism resulting in apoptosis of the injured neurons in the cerebral IRR that caspase-3 expression and activation abnormally increased by the reperfusion have more PARP rapidly inactivated by over-cleavage. z-DEVD-fmk may decrease PARP cleavage by inhibiting activity and auto-activation of caspase-3, and prevent the injured neurons from apoptosis.
    [Abstract] [Full Text] [Related] [New Search]