Journal article
Mechanism of post-translational modification by tyrosine phosphorylation of apoptotic proteins during hypoxia in the cerebral cortex of newborn piglets
Neurochemical research, v 35(1)
Jan 2010
PMID: 19597709
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The present study aims to investigate the mechanism of phosphorylation of apoptotic proteins and tests the hypothesis that the hypoxia-induced increased tyrosine phosphorylation of apoptotic proteins Bcl-2 and Bcl-xl is Ca(2+)-influx-dependent. Piglets were divided in normoxic (Nx, n = 5), hypoxic (Hx, n = 5) and hypoxic-pretreated with clonidine (Clo + Hx, n = 4) groups. Hypoxic animals were exposed to an FiO(2) of 0.06 for 1 h. Clonidine (12.5 microg/kg, IV) was administered to piglets 30 min prior to hypoxia. Hypoxia was confirmed by ATP and phosphocreatinine (PCr) levels. Cytosol was isolated and separated by 12% SDS-PAGE and probed with tyrosine phosphorylated (p) -Bax, Bad, Bcl-2 and Bcl-xl antibodies and bands were detected. The ATP levels (micromol/g brain) in the Nx, Hx, Clo + Hx were 4.3 +/- 1.0 (P < 0.05 vs. Hx, Clo-Hx), 0.9 +/- 0.8 and 1.5 +/- 0.3, respectively. The PCr levels in the Nx, Hx, Clo + Hx were 2.7 +/- 0.7 (P < 0.05 vs. Hx, Clo-Hx), 0.9 +/- 0.2 and 0.9 +/- 0.9, respectively. Ca(2+)-influx (pmoles/mg protein) was 4.96 +/- 0.94 in Nx, 11.11 +/- 2.38 in Hx, and 6.23 +/- 2.07 in Clo + Hx (P < 0.05 Nx vs. Hx and Hx vs. Clo + Hx). p-Bcl-2 density was 21.1 +/- 1.1 Nx, 58.9 +/- 9.6 Hx and 29.5 +/- 6.4 Clo + Hx (P < 0.05 vs. Hx). p-Bcl-xl density was 29.6 +/- 1.5 Nx, 50.6 +/- 7.4 Hx and 32.1 +/- 0.1 Clo + Hx (P < 0.05 vs. Hx). p-Bax density was 38.6 +/- 16.2 Nx, 46.1 +/- 5.5 Hx and 41.6 +/- 1.9 Clo + Hx groups (P = NS). p-Bad was 66.7 +/- 12.8 Nx, 71.2 +/- 6.8 Hx and 78.7 +/- 22.5 Clo + Hx groups (P = NS). Results showed that clonidine administration prior to hypoxia prevents the hypoxia-induced increased nuclear Ca(2+)-influx and increased phosphorylation of Bcl-2 and Bcl-xl while phosphorylation of Bad and Bax was not altered. We conclude that post-translational modification of anti-apoptotic proteins Bcl-2 and Bcl-xl during hypoxia is nuclear Ca(2+)-influx-dependent. We propose that blockade of nuclear Ca(2+)-influx that prevents phosphorylation of antiapoptotic proteins may become a neuroprotective strategy.
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Details
- Title
- Mechanism of post-translational modification by tyrosine phosphorylation of apoptotic proteins during hypoxia in the cerebral cortex of newborn piglets
- Creators
- Maria Delivoria-Papadopoulos - Drexel UniversityOm Prakash Mishra - Drexel University College of Medicine and St. Christopher’s Hospital for Children
- Publication Details
- Neurochemical research, v 35(1)
- Publisher
- Springer Nature
- Grant note
- HD-20337 / NICHD NIH HHS R56 HD038079 / NICHD NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000273093800009
- Scopus ID
- 2-s2.0-76849088588
- Other Identifier
- 991019169012904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences