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Effect of hyperoxia on serine phosphorylation of apoptotic proteins in mitochondrial membranes of the cerebral cortex of newborn piglets
Journal article   Peer reviewed

Effect of hyperoxia on serine phosphorylation of apoptotic proteins in mitochondrial membranes of the cerebral cortex of newborn piglets

Nadege A Brutus, Sarah Hanley, Qazi M Ashraf, Om P Mishra and Maria Delivoria-Papadopoulos
Neurochemical research, v 34(7), pp 1219-1225
Jul 2009
DOI: https://doi.org/10.1007/s11064-008-9898-z
PMID: 19169818
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Animals Animals, Newborn Apoptosis - drug effects Apoptosis - physiology bcl-2-Associated X Protein - metabolism bcl-Associated Death Protein - metabolism bcl-X Protein - metabolism Cerebral Cortex - drug effects Cerebral Cortex - metabolism Cerebral Cortex - ultrastructure Hyperoxia - physiopathology Mitochondrial Membranes - metabolism Phosphorylation Proto-Oncogene Proteins c-bcl-2 - metabolism Serine - metabolism Swine
Previous studies have shown that hyperoxia results in cerebral cortical neuronal apoptosis. Studies have also shown that phosphorylation of anti-apoptotic proteins Bcl-2 and Bcl-xl results in loss of their anti-apoptotic potential leading to alteration in mitochondrial membrane permeability and the release of apoptogenic proteins in the neuronal cell of the newborn piglets. The present study tests the hypothesis that cerebral hyperoxia will result in increased serine phosphorylation of apoptotic proteins Bcl-2, Bcl-xl, Bax, and Bad in the mitochondrial membranes of the cerebral cortex of newborn piglets. Twelve newborn piglets were divided into normoxic (Nx, n = 6) exposed to an FiO(2) of 0.21 for 1 h and hyperoxic (Hyx, n = 6) exposed to FiO(2) of 1.0 for 1 h. In the Hyx group, PaO(2) was maintained above 400 mmHg while the Nx group was kept at 80-100 mmHg. Cerebral cortical tissue was harvested and mitochondrial fractions were isolated. Mitochondrial membrane proteins were separated using 12% SDS-PAGE, and probed with anti-serine phosphorylated Bcl-2, Bcl-xl, Bax, and Bad antibodies. Protein bands were detected, analyzed by imaging densitometry and density expressed as absorbance (OD x mm(2)). Phosphorylated Bcl-2 (p-Bcl-2) protein density (OD x mm(2)) was 81.81 +/- 9.24 in Nx and 158.34 +/- 10.66 in Hyx (P < 0.05). Phosphorylated Bcl-xl (p-Bcl-xl) protein density was 52.98 +/- 3.59 in Nx and 99.62 +/- 18.22 in Hyx (P < 0.05). Phosphorylated Bax (p-Bax) protein was 161.13 +/- 6.27 in Nx and 174.21 +/- 15.95 in Hyx (P = NS). Phosphorylated Bad (p-Bad) protein was 166.24 +/- 9.47 in Nx 155.38 +/- 12.32 in Hyx (P = NS). The data show that there is a significant increase in serine phosphorylation of Bcl-2 and Bcl-xl proteins while phosphorylation of Bad and Bax proteins were not altered during hyperoxia in the mitochondrial fraction of the cerebral cortex of newborn piglets. We conclude that hyperoxia results in differential post-translational modification of anti-apoptotic proteins Bcl-2 and Bcl-xl as compared to pro-apoptotic proteins Bax and Bad in mitochondria. We speculate that phosphorylation of Bcl-2 and Bcl-xl will result in loss of their anti-apoptotic potential by preventing their dimerization with Bax leading to activation of the caspase cascade of neuronal death.

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Web of Science research areas
Biochemistry & Molecular Biology
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