title: Expression of Bax and Bcl-2 proteins during hypoxia in cerebral cortical neuronal nuclei of newborn piglets: effect of administration of magnesium sulfate.
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.
authors.affiliation: Department of Pediatrics, Division of Neonatology, St. Christopher's Hospital for Children, MCP Hahnemann University, Philadelphia, PA, USA. surav1@aol.com
authors.forename: S
authors.initials: S
authors.lastname: Ravishankar
authors.forename: Q M
authors.initials: QM
authors.lastname: Ashraf
authors.forename: K
authors.initials: K
authors.lastname: Fritz
authors.forename: O P
authors.initials: OP
authors.lastname: Mishra
authors.forename: M
authors.initials: M
authors.lastname: Delivoria-Papadopoulos
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008278:Magnesium Sulfate / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010725:Phosphocreatine / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013552:Swine; D051028:bcl-2-Associated X Protein
chemical_list: D002121:Calcium Channel Blockers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein; D010725:Phosphocreatine; D008278:Magnesium Sulfate; D000255:Adenosine Triphosphate