Exposure to an adverse intrauterine environment is recognized as an important risk factor for the development of cardiovascular disease later in life. Although oxidative stress has been proposed as a mechanism for the fetal programming phenotype, the role of mitochondrial O2•− (superoxide radical) production has not been explored. To determine whether mitochondrial ROS (reactive oxygen species) production is altered by in utero programming, pregnant ewes were given a 48-h dexamethasone (dexamethasone-exposed, 0.28 mg·kg−1 of body weight·day−1) or saline (control) infusion at 27–28 days gestation (term=145 days). Intact left ventricular mitochondria and freeze-thaw mitochondrial membranes were studied from offspring at 4-months of age. AmplexRed was used to measure H2O2 production. Activities of the antioxidant enzymes Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and catalase were measured. Compared with controls, a significant increase in Complex I H2O2 production was found in intact mitochondria from dexamethasone-exposed animals. The treatment differences in Complex I-driven H2O2 production were not seen in mitochondrial membranes. Consistent changes in H2O2 production from Complex III in programmed animals were not found. Despite the increase in H2O2 production in intact mitochondria from programmed animals, dexamethasone exposure significantly increased mitochondrial catalase activity, whereas Mn-SOD and GPx activities were unchanged. The results of the present study point to an increase in the rate of release of H2O2 from programmed mitochondria despite an increase in catalase activity. Greater mitochondrial H2O2 release into the cell may play a role in the development of adult disease following exposure to an adverse intrauterine environment.
Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria
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Nicholas H. von Bergen, Stacia L. Koppenhafer, Douglas R. Spitz, Kenneth A. Volk, Sonali S. Patel, Robert D. Roghair, Fred S. Lamb, Jeffrey L. Segar, Thomas D. Scholz; Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria. Clin Sci (Lond) 1 April 2009; 116 (8): 659–668. doi: https://doi.org/10.1042/CS20080474
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