Negative Regulation of Antioxidant Enzyme Gene Expression in the Developing Fetal Rat Lung by Prenatal Hormonal Treatments

Chen, You‐Wei; Whitney, Philip L.; Frank, Lee

doi:10.1203/00006450-199302000-00016

Cited by 17 publications

(9 citation statements)

References 18 publications

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“…cRNA preparation. The rat cRNA for Cu,ZnSOD, CAT, and GP were prepared as previously described (7,8). A pGEM-Blue construct a-actin cDNA (7) was used to synthesize a-actin [3H] cRNA for use as an mRNA recovery marker.…”

Section: Animals and Breedingmentioning

confidence: 99%

Differential Gene Expression of Antioxidant Enzymes in the Perinatal Rat Lung

Chen

Frank

1993

Pediatr Res

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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 G P 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 G P 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 G P they were not. At the time of birth, however, the mRNA levels of Cu,ZnSOD and CAT decreased -40%, whereas their enzyme activities increased. For MnSOD, only a slight rise in mRNA level was observed versus -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. (Pediatr Res 34: 27-31,1993)

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Section: Animals and Breedingmentioning

confidence: 99%

Differential Gene Expression of Antioxidant Enzymes in the Perinatal Rat Lung

Chen

Frank

1993

Pediatr Res

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“…Preparation of cRNA was performed as described previously (11,12). Total nucleic acids portionately with added mRNA.…”

Section: Biochemical Analysesmentioning

confidence: 99%

Failure of Premature Rabbits to Increase Lung Antioxidant Enzyme Activities after Hyperoxic Exposure: Antioxidant Enzyme Gene Expression and Pharmacologic Intervention with Endotoxin and Dexamethasone

et al. 1995

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Premature rabbits, unlike full-term rabbits, are unable to mount a protective increase in pulmonary antioxidant enzyme (AOE) activities in response to 48 h of hyperoxic exposure and demonstrate increased pulmonary 0, toxicity compared with full-term rabbits. To examine AOE gene expression of CuZn superoxide dismutase (SOD), Mn SOD, catalase, and glutathione peroxidase in preterm versus tcrm rabbits in response to hyperoxia, 29.5 d preterm rabbits (delivered by hysterotomy) and term rabbits (spontaneously vaginally delivered) were exposed to 48 h of >90% O2 or room air. Preterm rabbits had a significant increase in CuZn SOD rnRNA without corresponding AOE activity increases, suggesting translational1posttranslational inhibition. In full-term rabbits, the magnitude of lung AOE mRNA changes was associated with concordant magnitude changes in activities of CuZn SOD, Mn SOD, and catalase, suggesting pretranslational regulation of AOE gene expression; glutathione peroxidase, however, appears to be regulated translationally1 posttranslationally. To investigate potential pharmacologic means of overcoming the susceptibility of the preterm rabbit to 0, toxicity, 29.5 d preterm rabbits received 20-40 kgikg of Salmonella typhimurium endotoxin or diluent S.C. (after birth and at 24 h); in separate experiments, pregnant rabbits received intramuscular injections of dexarnethasone (0.01-0.05 mgikg) orThe incidence of chronic lung disease in human premature infants increases with decreasing gestational age (1) and is thought to be related in part to oxygen free radical-induced lung injury. In an attempt to explain the mechanisms involved with this chronic lung process and these epidemiologic observations, we have previously demonstrated that premature rabbits have decreased baseline activity levels of pulmonary AOE (2) and are also unable to mount a protective increase in AOE saline on gestational d 27.5 and 28.5 and undcrwent hysterotomy at 29.5 d. After hyperoxic exposurc, postnatal endotoxin trcatment of pretcrm rabbits resulted in significant increascs in CuZn SOD activity and CuZn SOD mRNA, suggesting a rcvcrsal of the translational/posttranslational inhibition characlcristic of the pretcrm rabbit, improved hyperoxic survival (74181 = 91% venc.~ls 70192 = 76%, p < 0.05; endotoxin versus controls), and protcction against hyperoxia-induced increases in lung lavage protein (+4% endotoxin versus +28% controls, 11 < 0.05). Prenatal dexamethasone neither improved hypcroxic survival, protcctcd against 0, toxicity, nor produced increases in any of the AOE aftcr 48 h of hyperoxia relative to air-breathing preterm rabbits. activities in response to 48-72 h of hyperoxic cxposure (3). Conversely, full-term newborn rabbits are able to significantly increase AOE activities with hyperoxia (3). Compared with term rabbits, which demonstrate minimal evidencc of hyperoxic lung damage, preterm rabbits manifest increases in sevcral indices of pulmonary 0, toxicity, including lung lavage fluid protein content, lung conjugated diene levels, and l...

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“…Our findings suggest that the regulation of lung AOE gene expression is complex under hyperoxic conditions. The prematurely delivered rats pretreated with TRH + DEX were previously found to have lowered lung AOE gene expression (depressed AOE activities and AOE mRNA levels) at preterm delivery at d 21 (4,5). Similarly, when examined at 2 d postnatal age after room air exposure, their pulmonary AOE mRNA levels remained lower in the premature TRH + DEX group compared with the shamtreated group.…”

Section: Survival In Hyperoxiamentioning

confidence: 84%

“…It has been previously demonstrated by our laboratories that although prenatal administration of TRH +DEX to pregnant rats accelerates surfactant system development in the late fetal lung, this same hormonal treatment significantly decreases the normal fetal lung AOE (SOD, CAT, and GP) activity elevations in late gestation (4). This hormonal effect appears to depend on a pretranslational/ transcriptional mechanism involving decreased AOE mRNA levels (5). When full-term newborn rats prenatally treated with TRH +DEX were exposed to prolonged hyperoxia, results showed that although these newborns manifested lower baseline AOE activities at birth than control term newborns, the 612 CHEN ETAL.…”

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confidence: 96%

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Positive Regulation of Pulmonary Antioxidant Enzyme Gene Expression by Prenatal Thyrotropin Releasing Hormone Plus Dexamethasone Treatment in Premature Rats Exposed to Hyperoxia

1995

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Prenatal administration of thyrotropin releasing hormone (TRH) plus dexamethasone (DEX) to pregnant rats produces significantly depressed fetal lung antioxidant enzyme (AOE) activities and AOE mRNA levels in late gestation. Because of this negative regulation of AOE gene expression in the late fetal lung, we hypothesized that hormonally pretreated prematurely delivered rats might demonstrate inferior tolerance to prolonged hyperoxia. Litters of prenatal TRH+DEX-treated and shamtreated prematurely delivered rat pups (gestational d 21 of 22) were randomized to either >95% O 2 or room air for up to 14 d. The right lungs of 2-and 7-d exposure pups were assayed for AOE activities; the left lungs of the same pups were used to quantitate the concentrations of AOE mRNA by solution hybridization. The prenatal TRH+ DEX-treated pups were able to induce adaptive lung AOE mRNA and activity responses to hyperoxia by 2 d of exposure; and by 7 d in O 2 they showed greater increases in AOE mRNA concentrations and AOE activities in response to hyperoxic challenge compared with the sham-treated controls. Lung lipid surfactant measurements after hyperoxia were not affected by prenatal TRH + DEX treatment. In addition, TRH + DEX-pretreated premature rats did not show the hypothesized increased susceptibility to 02-induced lung damage and lethality, but, in fact, had slightly improved hyperPrenatal hormonal therapy with maternal administration of a combination of TRH and glucocorticoids is now being extensively tested clinically in threatened premature deliveries to try to rapidly stimulate lung maturation and reduce the incidence and severity of respiratory distress syndrome in premature Received May 20, 1994; accepted December 1, 1994 oxic survival (d 3-7 of O 2 exposure) compared with shamtreated controls. Exposure to hyperoxia significantly reduced serum triiodothyronine and thyroxine levels in the sham-control pups. These findings suggest that although TRH + DEXpretreated premature rats have decreased lung AOE gene expression at the time of preterm delivery, subsequent hyperoxic exposure is able to convert AOE gene expression to positive regulation which results in more rapid and greater increases in protective AOE activity levels. This regulation is likely mediated differently for the individual AOE. (Pediatr Res 37: 611-616, 1995) Abbreviations TRH, thyrotropin releasing hormone DEX, dexamethasone AOE, antioxidant enzyme CuZnSOD, copper-zinc superoxide dismutase MnSOD, manganese superoxide dismutase CAT, catalase GP, glutathione peroxidase DSPC, disaturated phosphatidylcholine T3' triiodothyronine T 4 , thyroxine infants (1-3). It has been previously demonstrated by our laboratories that although prenatal administration of TRH +DEX to pregnant rats accelerates surfactant system development in the late fetal lung, this same hormonal treatment significantly decreases the normal fetal lung AOE (SOD, CAT, and GP) activity elevations in late gestation (4). This hormonal effect appears to depend on a pretranslational/ transcript...

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Negative Regulation of Antioxidant Enzyme Gene Expression in the Developing Fetal Rat Lung by Prenatal Hormonal Treatments

Cited by 17 publications

References 18 publications

Differential Gene Expression of Antioxidant Enzymes in the Perinatal Rat Lung

Differential Gene Expression of Antioxidant Enzymes in the Perinatal Rat Lung

Failure of Premature Rabbits to Increase Lung Antioxidant Enzyme Activities after Hyperoxic Exposure: Antioxidant Enzyme Gene Expression and Pharmacologic Intervention with Endotoxin and Dexamethasone

Positive Regulation of Pulmonary Antioxidant Enzyme Gene Expression by Prenatal Thyrotropin Releasing Hormone Plus Dexamethasone Treatment in Premature Rats Exposed to Hyperoxia

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