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  • Title: Expression of Bax and Bcl-2 proteins during hypoxia in cerebral cortical neuronal nuclei of newborn piglets: effect of administration of magnesium sulfate.
    Author: Ravishankar S, Ashraf QM, Fritz K, Mishra OP, Delivoria-Papadopoulos M.
    Journal: Brain Res; 2001 May 18; 901(1-2):23-9. PubMed ID: 11368946.
    Abstract:
    This study tests the hypothesis that administration of magnesium sulfate, an antagonist of the NMDA receptor ion-channel, will prevent the hypoxia-induced alteration in the expression and the ratio of Bax and Bcl-2 proteins in cerebral cortical neuronal nuclear membranes. Anesthetized, ventilated and instrumented newborn piglets were divided into three groups: normoxic controls (Nx), untreated hypoxic (Hx), and magnesium sulfate-treated hypoxic (Mg-Hx) groups. Cerebral hypoxia was induced by lowering the FiO2 (0.05-0.07) for 1 h and the cerebral cortex was harvested immediately for isolation of neuronal nuclei and hypoxia was confirmed biochemically by a decrease in the tissue levels of ATP and phosphocreatine (PCr). Brain tissue PCr (micromol/g brain) was 2.74+/-0.77 (Nx), 0.38+/-0.09 (Hx, P<0.05 vs. Nx) and 0.69+/-0.60 (Mg-Hx, P<0.05 vs. Nx). The density of immunoblotted proteins was expressed as absorbance (Axmm(2)). The expression of Bax protein (Axmm(2)) was 222+/-31 (Nx), 279+/-32 (Hx), and 148+/-44 (Mg-Hx, P<0.05 vs. Hx). Bcl-2 protein expression was 77+/-1.0 (Nx), 37+/-5.0 (Hx) and 46+/-15 (Mg-Hx, P<0.05 vs. Nx). The ratio of Bax to Bcl-2 proteins increased more than twofold during hypoxia as compared to normoxia (7:1 Hx vs. 3:1 Nx). However, in the magnesium sulfate-treated group the Bax:Bcl-2 ratio was similar to normoxic controls. The data demonstrate that magnesium sulfate treatment prevents both the hypoxia-induced increase in Bax protein expression and the alteration of Bax:Bcl-2 protein ratios. We suggest that magnesium sulfate treatment before and during hypoxia may decrease hypoxia-induced programmed cell death by maintaining the normal ratio of Bax to Bcl-2 proteins.
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