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Mechanism of DNA fragmentation during hypoxia in the cerebral cortex of newborn piglets
Journal article   Peer reviewed

Mechanism of DNA fragmentation during hypoxia in the cerebral cortex of newborn piglets

Ming-Chou Chiang, Qazi M Ashraf, Om P Mishra and Maria Delivoria-Papadopoulos
Neurochemical research, v 33(7), pp 1232-1237
Jul 2008
DOI: https://doi.org/10.1007/s11064-007-9574-8
PMID: 18253826
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Adenosine Triphosphate - metabolism Animals Animals, Newborn - physiology Apoptosis Regulatory Proteins - biosynthesis Apoptosis Regulatory Proteins - genetics Caspase 3 - metabolism Caspase 9 - physiology Caspase Inhibitors Cell Nucleus - drug effects Cell Nucleus - enzymology Cell Nucleus - metabolism Cerebral Cortex - metabolism Cytosol - drug effects Cytosol - enzymology Cytosol - metabolism Deoxyribonucleases - biosynthesis Deoxyribonucleases - genetics DNA Fragmentation Electrophoresis, Agar Gel Enzyme Activation - physiology Enzyme Inhibitors - pharmacology Hypoxia - metabolism Nerve Tissue Proteins - metabolism Neurons - metabolism Neurons - ultrastructure Oligopeptides - pharmacology Phosphocreatine - metabolism Swine
We have previously shown that hypoxia results in increased activity of caspase-9, caspase-3 and fragmentation of nuclear DNA in the cerebral cortex of newborn piglets. The present study tested the hypothesis that mechanism of DNA fragmentation during hypoxia in the cerebral cortex of newborn piglets is mediated by caspase-9-dependent caspase-3 activation. Newborn piglets were randomly assigned to normoxic, hypoxic, and hypoxic pretreated with a highly selective caspase-9 inhibitor, Z-LEHD-FMK groups. The data showed that cerebral tissue hypoxia results in increased expression of caspase-activated DNase (CAD) protein in the nucleus and fragmentation of nuclear DNA. A pretreatment with Z-LEHD-FMK attenuated the expression of CAD protein in the nucleus and the fragmentation of nuclear DNA. Based on these results, we conclude that the mechanism by which the nuclear DNA was fragmented is mediated by caspase-9-dependent caspase-3 activation and the consequence of caspase-activated DNase activation in the cerebral cortex of newborn piglets.

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Neurosciences
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