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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms that cause aging are not well understood. The oxidative stress hypothesis proposes that the changes associated with aging are a consequence of random oxidative damage to biomolecules. We hypothesized that oxidation of specific proteins is critical in controlling the rate of the aging process. Utilizing an immunochemical probe for oxidatively modified proteins, we show that mitochondrial aconitase, an enzyme in the citric acid cycle, is a specific target during aging of the housefly. The oxidative damage detected immunochemically was paralleled by a loss of catalytic activity of aconitase, an enzyme activity that is critical in energy metabolism. Experimental manipulations which decrease aconitase activity should therefore cause a decrease in life-span. This expected decrease was observed when flies were exposed to hyperoxia, which oxidizes aconitase, and when they were given fluoroacetate, an inhibitor of aconitase. The identification of a specific target of oxidative damage during aging allows for the assessment of the physiological age of a specific individual and provides a method for the evaluation of treatments designed to affect the aging process.
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PMID:Oxidative damage during aging targets mitochondrial aconitase. 932 80

The premature primate exposed to hyperoxia provides a useful model of bronchopulmonary dysplasia. A critical target in hyperoxic injury is the mitochondrial matrix enzyme aconitase. We hypothesized that this enzyme's activity would decline in the premature baboon lung during exposure to hyperoxia. Total aconitase activity was significantly decreased in the lungs of premature baboons of 140 days gestation with exposure to 100% oxygen for 6-10 days compared with as needed [pro re nada (PRN)] oxygen exposure and fetal controls (P = 0.0001). In activity gels, lungs from 100% oxygen-exposed animals (6-10 days) showed a nearly complete loss of mitochondrial aconitase activity relative to lungs from animals exposed only to PRN oxygen. Decreased lung aconitase activity was not a nonspecific effect of hyperoxia, causing mitochondrial damage or loss, because the activity of the mitochondrial respiratory enzyme cytochrome oxidase was not different in lungs of 100% oxygen-exposed relative to PRN oxygen-exposed newborns. In 125-day-gestation premature primates (age 6-10 days), lung total aconitase activity was correlated with inspired oxygen tension (r = 0.73 for fraction of inspired oxygen > 0.35), whereas, for animals of 140 days gestation, no such correlation was found. Thus the more premature animal's lung was more susceptible to loss of aconitase.
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PMID:Loss of lung mitochondrial aconitase activity due to hyperoxia in bronchopulmonary dysplasia in primates. 945 10

Friedreich ataxia (FA), the most common form of hereditary ataxia, is caused by a deficit in the mitochondrial protein frataxin. While several hypotheses have been suggested, frataxin function is not well understood. Oxidative stress has been suggested to play a role in the pathophysiology of FA, but this view has been recently questioned, and its link to frataxin is unclear. Here, we report the use of RNA interference (RNAi) to suppress the Drosophila frataxin gene (fh) expression. This model system parallels the situation in FA patients, namely a moderate systemic reduction of frataxin levels compatible with normal embryonic development. Under these conditions, fh-RNAi flies showed a shortened life span, reduced climbing abilities, and enhanced sensitivity to oxidative stress. Under hyperoxia, fh-RNAi flies also showed a dramatic reduction of aconitase activity that seriously impairs the mitochondrial respiration while the activities of succinate dehydrogenase, respiratory complex I and II, and indirectly complex III and IV are normal. Remarkably, frataxin overexpression also induced the oxidative-mediated inactivation of mitochondrial aconitase. This work demonstrates, for the first time, the essential function of frataxin in protecting aconitase from oxidative stress-dependent inactivation in a multicellular organism. Moreover our data support an important role of oxidative stress in the progression of FA and suggest a tissue-dependent sensitivity to frataxin imbalance. We propose that in FA, the oxidative mediated inactivation of aconitase, which occurs normally during the aging process, is enhanced due to the lack of frataxin.
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PMID:Causative role of oxidative stress in a Drosophila model of Friedreich ataxia. 1716 74