title: Chronic hypoxia impairs cytochrome oxidase activity via oxidative stress in selected fetal Guinea pig organs.
abstract: We hypothesized that chronic hypoxia disrupts mitochondrial function via oxidative stress in fetal organs. Pregnant guinea pig sows were exposed to either normoxia or hypoxia (10.5% O2, 14 days) in the presence or absence of the antioxidant, N-acetylcysteine (NAC). Near-term anesthetized fetuses were delivered via hysterotomy, and fetal livers, hearts, lungs, and forebrains harvested. We quantified the effects of chronic hypoxia on cytochrome oxidase (CCO) activity and 2 factors known to regulate CCO activity: malondialdehyde (MDA) and CCO subunit 4 (COX4). Hypoxia increased the MDA levels in fetal liver, heart, and lung with a corresponding reduction in CCO activity, prevented by prenatal NAC. The COX4 expression paralleled CCO activity in fetal liver and lung, but was unaltered in fetal hearts due to hypoxia. Hypoxia reduced the brain COX4 expression despite having no effect on CCO activity. This study identifies the mitochondrion as an important target site in tissue-specific oxidative stress for the induction of fetal hypoxic injury.
authors.affiliation: Department of Physiology, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Yazan M
authors.initials: YM
authors.lastname: Al-Hasan
authors.forename: LaShauna C
authors.initials: LC
authors.lastname: Evans
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Pinkas
authors.forename: Erinne R
authors.initials: ER
authors.lastname: Dabkowski
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
authors.forename: Loren P
authors.initials: LP
authors.lastname: Thompson
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005318:Fetal Heart / Q000196:embryology / Q000201:enzymology*; D006168:Guinea Pigs; D000860:Hypoxia / Q000201:enzymology*; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008168:Lung / Q000196:embryology / Q000201:enzymology*; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C519173:Cox4 protein, S cerevisiae; D003576:Electron Transport Complex IV