Journal article
Effect of hypoxia on expression of apoptotic proteins in nuclear, mitochondrial and cytosolic fractions of the cerebral cortex of newborn piglets: The role of nuclear Ca(++-)influx
Neurochemical research, v 33(7), pp 1196-1204
01 Jul 2008
PMID: 18293086
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We have shown that hypoxia results in increased influx of nuclear Ca++ and increased expression of nuclear apoptotic proteins. The present study tests the hypothesis that hypoxia alters the distribution of pro-apoptotic proteins Bad and Bax, and the anti-apoptotic proteins Bcl-xl, and Bcl-2 in the nuclear, mitochondrial and cytosolic compartments of the cerebral cortex of newborn piglets and the administration of Clonidine, an inhibitor of high affinity nuclear Ca++-ATPase, will prevent the hypoxia-induced increase in apoptotic proteins' expression. Studies were conducted in 19 newborn piglets, 6 normoxic (Nx), 7 hypoxic and 6 Clonidine-treated hypoxic (Hx-Clo). Tissue hypoxia was documented biochemically by measuring cerebral tissue ATP and phosphocreatine (PCr) levels. Bax and Bad protein expression increased in all the three compartments during hypoxia, while there was no significant change in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl. In Clonidine pretreated hypoxic group, the hypoxia-induced increased expression of pro-apoptotic proteins Bad and Bax was prevented in all the three fractions. We conclude that hypoxia results in increased expression of pro-apoptotic proteins in nuclear, mitochondrial and cytosolic compartments and that the increased expression of pro-apoptotic proteins during hypoxia is nuclear Ca++-influx-dependent. We propose that during hypoxia the increased ratio of (pro-apoptotic Bad and Bax/anti-apoptotic Bcl-xl and Bcl-2) in all the three compartments, will lead to altered mitochondrial and nuclear membrane permeability as well as caspase-9 activation in the cytosolic compartment.
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Details
- Title
- Effect of hypoxia on expression of apoptotic proteins in nuclear, mitochondrial and cytosolic fractions of the cerebral cortex of newborn piglets: The role of nuclear Ca(++-)influx
- Creators
- Maria Delivoria-Papadopoulos - Drexel UniversityQazi M. Ashraf - Drexel University College of Medicine and St. Christopher’s Hospital for ChildrenOm P. Mishra - Drexel University College of Medicine and St. Christopher’s Hospital for Children
- Publication Details
- Neurochemical research, v 33(7), pp 1196-1204
- Publisher
- Springer Nature
- Number of pages
- 9
- Grant note
- HD-20337; HD-38079 / NICHD NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) R56HD038079 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000256322300004
- Scopus ID
- 2-s2.0-44549086711
- Other Identifier
- 991019169811304721
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InCites Highlights
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences