Related Experiment Videos
Differential gene expression of antioxidant enzymes in the perinatal rat lung
Insights
Antioxidant enzyme gene expression in developing rat lungs is complex. Enzyme activities and mRNA levels do not always correlate, suggesting varied regulatory mechanisms during lung development.
Area of Science:
- Biochemistry
- Developmental Biology
- Pulmonology
Background:
- Developing rat lungs show increased catalase (CAT) and glutathione peroxidase (GP) activity late in gestation.
- Antioxidant enzymes (AOE) protect cells from oxidative stress, crucial during rapid lung development.
Purpose of the Study:
- To investigate if four major AOE (CAT, GP, copper-zinc SOD, manganese SOD) share similar developmental gene expression patterns in perinatal rat lungs.
- To determine if developmental regulation of AOE occurs at the pretranslational level.
Main Methods:
- Solution hybridization was used to measure AOE mRNA concentrations in perinatal rat lungs.
- AOE activities were assayed in the contralateral lungs of the same animals.
- Studies included fetal (18 days to term) and early postnatal rat pups.
Main Results:
- CAT and GP activities increased prenatally, while superoxide dismutase (SOD) activities showed varied patterns (Cu,ZnSOD declined, MnSOD constant).
- Postnatally, Cu,ZnSOD and CAT activities increased, MnSOD remained constant, and GP activity slightly declined.
- For Cu,ZnSOD, MnSOD, and CAT, mRNA levels generally paralleled activity changes, but not for GP.
- At birth, Cu,ZnSOD and CAT mRNA decreased significantly while activities increased; MnSOD mRNA slightly rose with a large activity increase.
Conclusions:
- Antioxidant enzymes in the developing rat lung are not coordinately regulated.
- Developmental regulation of AOE gene expression is complex, involving multiple regulatory levels beyond mRNA concentration.
Abstract:
It has been previously demonstrated that the developing rat lung markedly increases its catalase (CAT) and glutathione peroxidase (GP) activities during the final 10 to 15% of gestation. In the present studies, we tested whether four major antioxidant enzymes (AOE) in perinatal rat lungs might share a similar pattern of developmental AOE gene expression via a pretranslational mechanism. The left lungs of 18-d to term fetuses and early postnatal rat pups were used to measure the concentrations of AOE mRNA by solution hybridization and the right lungs of the same group of animals were assayed for AOE activities. Results revealed differential AOE gene expression in developing rat lungs. Whereas the CAT and GP activities progressively increased prenatally, the superoxide dismutase (SOD) activity either declined [copper-zinc SOD (Cu, ZnSOD)] or remained constant [manganese SOD (MnSOD)] in late gestation. Postnatally, Cu,ZnSOD and CAT activities progressively increased, whereas MnSOD remained constant and GP activity declined slightly. For Cu,ZnSOD, MnSOD, and CAT, the activity changes were generally consistent with the patterns of changes in their mRNA concentrations in both the prenatal and postnatal period, but for GP they were not. At the time of birth, however, the mRNA levels of Cu,ZnSOD and CAT decreased approximately 40%, whereas their enzyme activities increased. For MnSOD, only a slight rise in mRNA level was observed versus approximately 100% increase in its activity at the time of birth. These findings suggest that the AOE are not coordinately regulated, and that developmental regulation of AOE gene expression in the perinatal rat lung is complex and likely exerted at different levels of regulation.