Effects of postnatal steroids on Na+/K+-ATPase activity and alpha1- and beta1-subunit protein expression in the cerebral cortex and renal cortex of newborn lambs.
| Title: | Effects of postnatal steroids on Na+/K+-ATPase activity and alpha1- and beta1-subunit protein expression in the cerebral cortex and renal cortex of newborn lambs. |
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| Authors: | Kim CR; Pediatrics, Women & Infants' Hospital of Rhode Island and Brown Medical School, Providence, RI 02905-2499, USA.; Sadowska GB; Petersson KH; Merino M; Sysyn GD; Padbury JF; Stonestreet BS |
| Source: | Reproduction, fertility, and development [Reprod Fertil Dev] 2006; Vol. 18 (4), pp. 413-23. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: Commonwealth Scientific and Industrial Research Organisation Country of Publication: Australia NLM ID: 8907465 Publication Model: Print Cited Medium: Print ISSN: 1031-3613 (Print) Linking ISSN: 10313613 NLM ISO Abbreviation: Reprod Fertil Dev Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: East Melbourne, Vic., Australia : Commonwealth Scientific and Industrial Research Organisation, c1989- |
| MeSH Terms: | Animals, Newborn* ; Sheep*; Adrenal Cortex Hormones/*administration & dosage ; Cerebral Cortex/*enzymology ; Kidney Cortex/*enzymology ; Sodium-Potassium-Exchanging ATPase/*metabolism; Adenosine Triphosphate/metabolism ; Dexamethasone/administration & dosage ; Protein Subunits/analysis ; Animals ; Blotting, Western ; Body Weight ; Dose-Response Relationship, Drug ; Organ Specificity ; Placebos |
| Abstract: | Na(+)/K(+)-ATPase is a membrane-bound enzyme responsible for Na(+)/K(+) translocation across cell membranes. It is essential for the generation of electrochemical gradients, which control the ionic environment necessary for electrical activity and water and electrolyte balance. Newborn infants who are at risk of developing bronchopulmonary dysplasia (BPD) are frequently treated with corticosteroids. Although these infants are at risk for neurological, water and electrolyte abnormalities, there is little information regarding the effects of clinically relevant doses of corticosteroids on Na(+)/K(+)-ATPase activity and protein isoform expression in the brain and kidney of newborns. In the present study, we examined the effects of dexamethasone on cerebral cortical and renal cortical Na(+)/K(+)-ATPase activity and alpha1- and beta1-protein isoform expression in newborn lambs. Lambs were given four injections of a placebo (n = 11) or one of three different doses of dexamethasone (0.01 mg kg(-1), n = 9; 0.25 mg kg(-1), n = 11; or 0.50 mg kg(-1), n = 9) 12 h apart on Postnatal Days 3 and 4 up to 18 h before harvest of the cerebral cortex and renal cortex. We selected doses in a range to approximate those used to treat infants with BPD. Na(+)/K(+)-ATPase activity was measured in membrane preparations as ouabain-sensitive inorganic phosphate liberation from ATP and alpha1- and beta1-subunit abundance by Western immunoblot. Postnatal treatment of lambs with dexamethasone resulted in a 21.4% increase in Na(+)/K(+)-ATPase activity and a 30.4% increase in catalytic alpha1-protein expression in the cerebral cortex at a dose of 0.50 mg kg(-1) dexamethasone, but not at the lower doses. Dexamethasone treatment was not associated with changes in beta1-isoform expression in the cerebral cortex. In the kidney, dexamethasone treatment was not associated with significant changes in Na(+)/K(+)-ATPase activity or alpha1- or beta1-isoform expression for the doses we examined. Therefore, clinically relevant corticosteroid treatment exerts dose-related, differential organ-specific effects on Na(+)/K(+)-ATPase activity and protein isoform expression in newborn lambs. |
| Grant Information: | R01-HD-34618 United States HD NICHD NIH HHS |
| Substance Nomenclature: | 0 (Adrenal Cortex Hormones); 0 (Placebos); 0 (Protein Subunits); 7S5I7G3JQL (Dexamethasone); 8L70Q75FXE (Adenosine Triphosphate); EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase) |
| Entry Date(s): | Date Created: 20060602 Date Completed: 20060623 Latest Revision: 20191210 |
| Update Code: | 20260130 |
| DOI: | 10.1071/rd05114 |
| PMID: | 16737634 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural