Faculty Collaboration Database

Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria. Clin Sci (Lond) 2009 Apr;116(8):659-68

Date

11/27/2008

Pubmed ID

19032144

Pubmed Central ID

PMC3677965

DOI

10.1042/CS20080474

Scopus ID

2-s2.0-66949132569 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

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 O(2)(*-) (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 H(2)O(2) 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 H(2)O(2) production was found in intact mitochondria from dexamethasone-exposed animals. The treatment differences in Complex I-driven H(2)O(2) production were not seen in mitochondrial membranes. Consistent changes in H(2)O(2) production from Complex III in programmed animals were not found. Despite the increase in H(2)O(2) 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 H(2)O(2) from programmed mitochondria despite an increase in catalase activity. Greater mitochondrial H(2)O(2) release into the cell may play a role in the development of adult disease following exposure to an adverse intrauterine environment.

Author List

von Bergen NH, Koppenhafer SL, Spitz DR, Volk KA, Patel SS, Roghair RD, Lamb FS, Segar JL, Scholz TD

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antioxidants
Disease Models, Animal
Electron Transport Complex I
Electron Transport Complex III
Female
Fetal Development
Hydrogen Peroxide
Male
Mitochondria, Heart
Mitochondrial Membranes
Oxidative Phosphorylation
Oxygen Consumption
Reactive Oxygen Species
Sheep