title: 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.
abstract: 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.
  
  
  OBJECTIVE
  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 PaCO(2) of 11-15 mm Hg; normocapnic (N, n = 5), ventilated at a PaCO(2) of 40 mm Hg; and corrected normocapnic (CN, n = 4), ventilated as H with CO(2) 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.
authors.affiliation: Division of Pulmonology, Department of Pediatrics, University of Maryland, Baltimore, MD 21201 , USA. alasso@peds.umaryland.edu
authors.forename: Anayansi
authors.initials: A
authors.lastname: Lasso Pirot
authors.forename: Karen I
authors.initials: KI
authors.lastname: Fritz
authors.forename: Qazi M
authors.initials: QM
authors.lastname: Ashraf
authors.forename: Om P
authors.initials: OP
authors.lastname: Mishra
authors.forename: Maria
authors.initials: M
authors.lastname: Delivoria-Papadopoulos
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000166:cytology*; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000378:metabolism; D016857:Hypocapnia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D013552:Swine; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D051028:bcl-2-Associated X Protein