Journal article
Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria
Clinical science (1979), Vol.116(8), pp.659-668
04/2009
DOI: 10.1042/CS20080474
PMCID: PMC3677965
PMID: 19032144
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.
Details
- Title: Subtitle
- Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria
- Creators
- Nicholas H Von Bergen - Department of Pediatrics, Department of Radiation Oncology, Carver College of Medicine, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242, U.S.AStacia L Koppenhafer - Department of Pediatrics, Department of Radiation Oncology, Carver College of Medicine, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242, U.S.ADouglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Carver College of Medicine, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242, U.S.AKenneth A Volk - Department of Pediatrics, Department of Radiation Oncology, Carver College of Medicine, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242, U.S.ASonali S Patel - Department of Pediatrics, Department of Radiation Oncology, Carver College of Medicine, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242, U.S.ARobert D Roghair - Department of Pediatrics, Department of Radiation Oncology, Carver College of Medicine, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242, U.S.AFred S Lamb - Department of Pediatrics, Department of Radiation Oncology, Carver College of Medicine, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242, U.S.AJeffrey L Segar - Department of Pediatrics, Department of Radiation Oncology, Carver College of Medicine, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242, U.S.AThomas D Scholz - Department of Pediatrics, Department of Radiation Oncology, Carver College of Medicine, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242, U.S.A
- Resource Type
- Journal article
- Publication Details
- Clinical science (1979), Vol.116(8), pp.659-668
- DOI
- 10.1042/CS20080474
- PMID
- 19032144
- PMCID
- PMC3677965
- NLM abbreviation
- Clin Sci (Lond)
- ISSN
- 0143-5221
- eISSN
- 1470-8736
- Grant note
- P30 CA086862 || CA / National Cancer Institute : NCI K08 HD050359 || HD / National Institute of Child Health & Human Development : NICHD R21 ES012268 || ES / National Institute of Environmental Health Sciences : NIEHS R01 CA100045 || CA / National Cancer Institute : NCI
- Language
- English
- Date published
- 04/2009
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics; Pathology; Hematology/Oncology; Radiation Oncology; Child and Community Health; Neonatology
- Record Identifier
- 9984047755202771
Metrics
40 Record Views