Nimodipine modulates Bcl-2 and Bax mRNA expression after cerebral ischemia

Abstract

In order to explore whether the member of Bcl-2 gene family, for example, Bcl-2 and Bax, are induced after cerebral ischemia, and whether expression of genes can be modulated by calcium-antagonist, the rat cerebral ischemic models were made by occluding left middle cerebral artery. The expression of Bcl-2 and Bax mRNA was measured by RT-PCR method. After middle cerebral artery occlusion (MCAO), the expression of both Bcl-2 and Bax mRNA were induced. Level of Bcl-2 mRNA increased steadily and level of Bax mRNA increased gradually at first, reached a peak after 24 h, then decreased slowly. After administration of nimodipine, Bcl-2 mRNA was up-regulated in the hippocampus 6 and 24h after ischemia, while Bax mRNA was down-regulated 6 and 24 h after ischemia. Focal cerebral ischemia can induce proto-oncogenes to express, which was associated with apoptosis. Calcium-antagonist can up-regulate Bcl-2 mRNA and down-regulate Bax mRNA. The increased ratio of Bcl-2 and Bax mRNA may contribute to the anti-apoptic effect of nimodipine. The study indicates that pharmacological modulation of Bcl-2 family member expression could become a new strategy to manage neuronal damage.

Keywords

cerebral ischemia / nimodipine / modulate / Bcl-2 and Bax mRNA

References

[1] ZhouJ G, LiuJ C, FangY Q. Effect of hyperbaric oxygen on the expression of proteins Bcl-2 and Bax in the gerbil hippocampus CA1 following forebrain ischemia reperfusion. J Chin Appl Physiol (Chinese), 2000, 16298-298

[2] CindyM, YamamotoA, AmiyaP, et al. . Redistribution of Bax is a early step in a apoptotic pathway leading to germ cell death in rats, triggered by mild testicular hyperthermia. Biol Reprod, 2000, 631683-1683

[3] BrambrinkA M, SchneiderA, NogaH, et al. . Tolerance-Inducing dose of 3-nitropropionic acid modulates bcl-2 and bax balance in the rat brain: a potential mechanism of chemical preconditioning. J Cereb Blood Flow Metab, 2000, 201425-1425

[4] KatsuyukiK, SatoshiK, Takayuki, et al. . Apoptotic DNA fragmentation and upregulation of bax induced by transient ischemia of the rat retina. Brain Res, 1999, 81511-11

[5] PuC Q, LangS Y, WuW P. Cerebrovascular Diseases, 1999, Beijing, People's Publication House of Militry Medicine: 141-144

[6] BotezG, RamiA. Immunoreactivity for Bcl-2 and C-Jun/AP1 in hippocampal corpora amylacea after ischaemia in humans. Neuropathol Appl Neurobiol, 2001, 27474-474

[7] NilsonC W, WieE P, PovlishockJT, et al. . Oxygen radicals in cerebral ischemia. Am J Physiol, 1998, 2631356-1356

[8] ChoiJ M, ShinH K, KimK Y, et al. . Neuroprotective effect of cilostazol against focal cerebral ischemia via antiapoptotic action in rats. J Pharmacol Exp Ther, 2002, 300787-787

[9] SiesjoB, KatsuraK I, SmithM L. Mechanisms of secondary brain damage in global and focal ischemia: a speculative synthesis. J Neurotrauma, 1995, 12943-943