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Effects of Severe Hypocapnia on Expression of Bax and Bcl-2 Proteins, DNA Fragmentation, and Membrane Peroxidation Products in Cerebral Cortical Mitochondria of Newborn Piglets
Journal article   Peer reviewed

Effects of Severe Hypocapnia on Expression of Bax and Bcl-2 Proteins, DNA Fragmentation, and Membrane Peroxidation Products in Cerebral Cortical Mitochondria of Newborn Piglets

Anayansi Lasso Pirot, Karen I Fritz, Qazi M Ashraf, Om P Mishra and Maria Delivoria-Papadopoulos
Neonatology (Basel, Switzerland), v 91(1), pp 20-27
Jan 2007
PMID: 17344648

Abstract

Original Paper
Background: Hypocapnia occurs in the newborn infant inadvertently or as a therapeutic modality and may result in neuronal and mitochondrial alterations in the newborn brain. Since mitochondria regulate apoptosis, these alterations may initiate a cascade of reactions that lead to apoptotic cell death. Objectives: This study tests the hypothesis that hypocapnia results in increased expression of the pro-apoptotic protein Bax, fragmentation of DNA and membrane lipid peroxidation in cerebral cortical mitochondria (mt) of newborn piglets. Methods: Studies were performed in three groups of anesthetized normoxic newborn piglets: hypocapnic (H, n = 5), ventilated at a PaCO2 of 11–15 mm Hg; normocapnic (N, n = 5), ventilated at a PaCO2 of 40 mm Hg; and corrected normocapnic (CN, n = 4), ventilated as H with CO2 added to maintain normocapnia. Tissue ATP and phosphocreatine levels were determined. Mitochondrial membrane proteins were separated, transblotted and probed with antibodies to Bax and Bcl-2. Bands were detected by enhanced chemiluminescence and analyzed by imaging densitometry. mtDNA was isolated. Cell and mitochondrial membrane lipid peroxidation products were measured spectrofluorometrically. Results: ATP and PCr concentrations were similar in the 3 groups. The ratio of Bax/Bcl-2 increased significantly in H compared to N and CN. mtDNA fragmentation was also significantly greater in H compared to N or CN. Membrane lipid peroxidation was higher in H than in N or CN; and in CN compared to N. Conclusions: The data demonstrate that severe hypocapnia results in increased Bax expression, DNA fragmentation, and membrane lipid peroxidation in mitochondria of cerebral cortical neurons of newborn piglets, and may result in apoptotic cell death.

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Collaboration types
Domestic collaboration
Web of Science research areas
Pediatrics
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