Restricted accessResearch articleFirst published online 2009-03
Na +,K+-ATPase Activity and Subunit Isoform Protein Abundance: Effects of Antenatal Glucocorticoids in the Frontal Cerebral Cortex and Renal Cortex of Ovine Fetuses
We examined the effects of single and multiple maternal glucocorticoid courses on cerebral cortical (CC) and renal cortical (RC) Na+,K+-ATPase activity and protein isoform abundance in fetal sheep. Ewes received four dexamethasone or placebo injections in the single course (SC) groups, and the same treatment once a week for five-weeks in the multiple course (MC) groups. CC Na +,K+-ATPase a2-abundance was higher (P<0.05) and β2-abundance lower in the SC dexamethasone than placebo group, but Na+,K+-ATPase activity did not change. CC Na+,K+-ATPase activity, a1-, β1 -, and β2-abundance were lower in the MC dexamethasone than placebo group, but a2- and a3-abundance did not change. Both dexamethasone courses did not affect CC cell number. RC Na +,K+-ATPase activity, a1- and β1 -abundance were higher in the MC dexamethasone than placebo group, but did not change in the SC dexamethasone group. We conclude MC, but not a SC of dexamethasone, affect fetal cerebral and renal Na+,K+-ATPase, and MC result in differential effects on Na+,K+-ATPase in these organs.
Therien AG, Blostein R.Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol . 2000;279:C541-C566.
3.
Malik N., Canfield VA, Beckers MC, Gros P., Levenson R.Identification of the mammalian Na,K-ATPase 3 subunit. J Biol Chem. 1996;271:22754-22758.
4.
Mobasheri A. , Avila J., Cozar-Castellano I., et al. Na+, K+-ATPase isozyme diversity; comparative biochemistry and physiological implications of novel functional interactions. Biosci Rep. 2000;20:51-91.
5.
Chow DC, Forte JGFunctional significance of the beta-subunit for heterodimeric P-type ATPases . J Exp Biol. 1995;198 (pt 1):1-17.
6.
Horisberger JD, Lemas V., Kraehenbuhl JP, Rossier BCStructure-function relationship of Na,K-ATPase . Annu Rev Physiol. 1991;53:565-584.
7.
Hieber V., Siegel GJ, Fink DJ, Beaty MW, Mata M.Differential distribution of (Na, K)-ATPase alpha isoforms in the central nervous system. Cell Mol Neurobiol. 1991;11:253-262.
8.
Shull GE, Greeb J., Lingrel JBMolecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain. Biochemistry. 1986;25:8125-8132.
9.
Herrera VL, Cova T., Sassoon D., Ruiz-Opazo.Developmental cell-specific regulation of Na(+)-K(+)-ATPase alpha 1-, alpha 2-, and alpha 3-isoform gene expression. Am J Physiol. 1994 ;266 (5 pt 1):C1301-C1312.
10.
Lucking K., Nielsen JM, Pedersen PA, Jorgensen PLNa-K-ATPase isoform (alpha 3, alpha 2, alpha 1) abundance in rat kidney estimated by competitive RT-PCR and ouabain binding. Am J Physiol. 1996;271 (2) Pt 2:F253-60.
11.
Orlowski J. , Lingrel JBTissue-specific and developmental regulation of rat Na,K-ATPase catalytic alpha isoform and beta subunit mRNAs. J Biol Chem. 1988;263:10436-10442.
12.
Jaisser F., Jaunin P., Geering K., Rossier BC, Horisberger JDModulation of the Na,K-pump function by beta subunit isoforms. J Gen Physiol. 1994;103:605-623.
13.
Aperia A., Larsson L., Zetterstrom R.Hormonal induction of Na-K-ATPase in developing proximal tubular cells. Am J Physiol. 1981;241:F356-F360.
14.
Celsi G., Wang ZM, Akusjarvi G., Aperia A.Sensitive periods for glucocorticoids' regulation of Na+,K(+)-ATPase mRNA in the developing lung and kidney. Pediatr Res. 1993;33:5-9.
15.
Petershack JA, Nagaraja SC, Guillery ENRole of glucocorticoids in the maturation of renal cortical Na+-K+-ATPase during fetal life in sheep. Am J Physiol. 1999;276 (6 pt 2):R1825-R1832.
16.
Devarajan P. , Benz EJ, Jr.Translational regulation of Na-K-ATPase subunit mRNAs by glucocorticoids. Am J Physiol Renal Physiol . 2000;279:F1132-F1138.
17.
Crowley PAAntenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol.1995;173:322-335.
18.
Doyle LW, Kitchen WH, Ford GW, Rickards AL, Lissenden JV, Ryan MMEffects of antenatal steroid therapy on mortality and morbidity in very low birth weight infants. J Pediatr. 1986;108:287-292.
19.
Liggins GC, Howie RNA controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics . 1972;50: 515-525.
20.
National Institutes of Health Consensus Development Panel.NIH consensus development panel on the effect of corticosteroids for fetal maturation on perinatal outcomes. JAMA. 1995;273:413-418.
21.
Crowther CA, Harding JERepeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database Syst Rev.CD003935.
22.
Stiles ADPrenatal corticosteroids-early gain, long-term questions. N Engl J Med. 2007;357:1248-1250.
23.
National Institutes of Health Consensus Development Panel.Antenatal Corticosteroids Revisited: Repeat Courses.2000;17:1-18.
24.
Crowther CA , Haslam RR, Hiller JE, Doyle LW, Robinson JS, and the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) Study Group.Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial. Lancet. 2006;367:1913-1919.
25.
Wapner RJ, Sorokin Y., Thom EA, et al. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Am J Obstet Gynecol. 2006;195:633-642.
26.
Wapner RJ, Sorokin Y., Mele L., et al. Long-term outcomes after repeat doses of antenatal corticosteroids . N Engl J Med. 2007;357:1190-1198.
27.
Berry LM, Polk DH, Ikegami M., Jobe AH, Padbury JF, Ervin MGPreterm newborn lamb renal and cardiovascular responses after fetal or maternal antenatal betamethasone. Am J Physiol. 1997 ;272 (6 pt 2):R1972-R1979.
28.
Okah FA, Pickens WL, Hoath SBEffect of prenatal steroids on skin surface hydrophobicity in the premature rat. Pediatr Res. 1995;37 (4 pt 1):402-408.
29.
Stonestreet BS, Hansen NB, Laptook AR, Oh W.Glucocorticoid accelerates renal functional maturation in fetal lambs. Early Hum Dev. 1983;8:331-341.
30.
Stonestreet BS, Petersson KH, Sadowska GB, Pettigrew KD, Patlak CSAntenatal steroids decrease blood-brain barrier permeability in the ovine fetus. Am J Physiol. 1999;276 (2 pt 2): R283-R289.
31.
Adams DF, Ment LR, Vohr B.Antenatal therapies and the developing brain. Semin Neonatol . 2001;6:173-183.
32.
Schwab M., Antonow-Schlorke I., Kuhn B., et al. Effect of antenatal betamethasone treatment on microtubuleassociated proteins MAP1B and MAP2 in fetal sheep. J Physiol. 2001;530 (pt 3):497-506.
33.
Schwab M., Roedel M., Anwar MA, et al. Effects of betamethasone administration to the fetal sheep in late gestation on fetal cerebral blood flow. J Physiol. 2000;528 (pt 3): 619-632.
34.
Schwab M., Schmidt K., Roedel M., et al. Non-linear changes of electrocortical activity after antenatal betamethasone treatment in fetal sheep. J Physiol. 2001;531 (pt 2):535-543.
35.
Stonestreet BS, Elitt CM, Markowitz J., Petersson KH, Sadowska GBEffects of antenatal corticosteroids on regional brain and non-neural tissue water content in the ovine fetus. J Soc Gynecol Investig. 2003;10:59-66.
36.
Stonestreet BS, Sadowska GB, McKnight AJ, Patlak C., Petersson KHExogenous and endogenous corticosteroids modulate blood-brain barrier development in the ovine fetus. Am J Physiol Regul Integr Comp Physiol. 2000;279:R468-R477.
37.
Dunlop SA, Archer MA, Quinlivan JA, Beazley LD, Newnham JPRepeated prenatal corticosteroids delay myelination in the ovine central nervous system. J Matern Fetal Med. 1997;6:309-313.
38.
Huang WL, Harper CG, Evans SF, Newnham JP, Dunlop SARepeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep. Int J Dev Neurosci. 2001;19:415-425.
39.
Dodic M., Wintour EMEffects of prolonged (48 h) infusion of cortisol on blood pressure, renal function and fetal fluids in the immature ovine foetus. Clin Exp Pharmacol Physiol. 1994;21:971-980.
40.
Wintour EM, Alcorn D., McFarlane A., Moritz K., Potocnik SJ, Tanqalakis K.Effect of maternal glucocorticoid treatment on fetal fluids in sheep at 0.4 gestation. Am J Physiol. 1994;266 (4 pt 2):R1174-R1181.
41.
Dickinson H. , Walker DW, Wintour EM, Moritz K.Maternal dexamethasone treatment at midgestation reduces nephron number and alters renal gene expression in the fetal spiny mouse. Am J Physiol Regul Integr Comp Physiol.2007;292: R453-R461. Epub 2006 Aug 31.
42.
al-Dahan J. , Stimmler L., Chantler C., Haycock GBThe effect of antenatal dexamethasone administration on glomerular filtration rate and renal sodium excretion in premature infants . Pediatr Nephrol. 1987;1:131-135.
43.
Omar SA, DeCristofaro JD, Agarwal BI, La Gamma EFEffects of prenatal steroids on water and sodium homeostasis in extremely low birth weight neonates. Pediatrics. 1999 ;104 (3 pt 1):482-488.
44.
Sadowska GB , Patlak CS, Petersson KH, Stonestreet BSEffects of multiple courses of antenatal corticosteroids on blood-brain barrier permeability in the ovine fetus. J Soc Gynecol Investig. 2006;13(4):248-255.
45.
Stonestreet BS, Watkins S., Petersson KH, Sadowska GBEffects of multiple courses of antenatal corticosteroids on regional brain and somatic tissue water content in ovine fetuses. J Soc Gynecol Investig. 2004;11:166-174.
46.
Jorgensen PLPurification and characterization of (Na+ plus K+)-ATPase. 3. Purification from the outer medulla of mammalian kidney after selective removal of membrane components by sodium dodecylsulphate. Biochim Biophys Acta.1974;356:36-52.
47.
Lo SC, August TR, Liberman UA, Edelman ISDependence of renal (Na+ + k+)-adenosine triphosphatase activity on thyroid status. J Biol Chem. 1976;251:7826-7833.
48.
Schmitt CA, McDonough AADevelopmental and thyroid hormone regulation of two molecular forms of Na+-K+-ATPase in brain. J Biol Chem. 1986;261:10439-10444.
Kim CR, Sadowska GB, Petersson KH, Merino M., Sysyn GD, Padbury JF, Stonestreet BSEffects 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 . Reprod Fertil Dev. 2006;18: 413-423.
51.
Martin-Vasallo P., Wetzel RK, Garcia-Segura LM, Molina-Holgado E., Aryarkhova E., Sweadner KJOligodendrocytes in brain and optic nerve express the beta3 subunit isoform of Na,K-ATPase . Glia. 2000;31:206-218.
52.
Arystarkhova E., Sweadner KJTissue-specific expression of the Na,K-ATPase beta3 subunit. The presence of beta3 in lung and liver addresses the problem of the missing subunit. J Biol Chem.1997;272:22405-22408.
53.
Malaeb SN, Sadowska GB, Stonestreet BSEffects of maternal treatment with corticosteroids on tight junction protein expression in the cerebral cortex of the ovine fetus with and without exposure to in utero brain ischemia. Brain Res. 2007 ;1160:11-19.
54.
Ron NP, Kazianis JA, Padbury JF, Brown CM, McGonnigal BG, Sysyn GD, Sadowska GB, Stonestreet BSOntogeny and the effects of corticosteroid pretreatment on aquaporin water channels in the ovine cerebral cortex. Reprod Fertil Dev. 2005;17:535-542.
55.
Uno H., Lohmiller L., Thieme C., Kemnitz JW, Engle MJ, Roecker EB, Farrell PMBrain damage induced by prenatal exposure to dexamethasone in fetal rhesus macaques. I. Hippocampus. Brain Res Dev Brain Res.1990;53: 157-167.
56.
Mullen RJ, Buck CR, Smith AMNeuN, a neuronal specific nuclear protein in vertebrates. Development. 1992;116:201-211.
57.
Sliwowska JH , Billings HJ, Goodman RL, Coolen LM, Lehman MNThe premammillary hypothalamic area of the ewe: anatomical characterization of a melatonin target area mediating seasonal reproduction. Biol Reprod. 2004;70: 1768-1775.
58.
Feraille E. , Doucet A.Sodium-potassiumadenosinetriphosphatase-dependent sodium transport in the kidney: hormonal control. Physiol Rev. 2001;81:345-418.
59.
Patrick J., Hilton PJCharacterization of sodium-transport disorders in disease: different effects upon sodium and potassium of changes in the sodium pump and in membrane permeability . Clin Sci (Lond). 1979;57:289-293.
60.
Rose AM, Valdes R. Jr.Understanding the sodium pump and its relevance to disease. Clin Chem. 1994;40:1674-1685.
61.
Jamme I., Petit E., Gerbi A., Maxient JM, MacKenzie ET, Nouvelot A.Changes in ouabain affinity of Na+, K+-ATPase during focal cerebral ischaemia in the mouse. Brain Res. 1997;774:123-130.
62.
Chauhan NB, Lee JM, Siegel GJNa,K-ATPase mRNA levels and plaque load in Alzheimer's disease. J Mol Neurosci. 1997;9:151-66.
63.
Hieber V., Siegel GJ, Fink DJ, Beaty MW, Mata M.Differential distribution of (Na, K)-ATPase alpha isoforms in the central nervous system. Cell Mol Neurobiol. 1991;11:253-262.
64.
Shyjan AW, Levenson R.Antisera specific for the alpha 1, alpha 2, alpha 3, and beta subunits of the Na,K-ATPase: differential expression of alpha and beta subunits in rat tissue membranes. Biochemistry. 1989;28:4531-4535.
65.
Watts AG, Sanchez-Watts G., Emanuel JR, Levenson R.Cell-specific expression of mRNAs encoding Na+,K(+)-ATPase alpha- and beta-subunit isoforms within the rat central nervous system. Proc Natl Acad Sci U S A.1991;88:7425-7429.
66.
Jobe AH, Polk DH, Ervin MG, Padbury JF, Rebello CM, Ikegami M.Preterm betamethasone treatment of fetal sheep: outcome after term delivery . J Soc Gynecol Investig. 1996;3: 250-258.
67.
Smith LM, Altamirano AK, Ervin MG, Seidner SR, Jobe AHPrenatal glucocorticoid exposure and postnatal adaptation in premature newborn baboons ventilated for six days. Am J Obstet Gynecol. 2004;191:1688-1694.
68.
Horvath K., Blochin B., Hill I., Verma R., Lu RB, Lebenthal E.The pre- and postnatal development of Na+/K(+)-ATPase in gastrointestinal organs of the rat: effect of betamethasone treatment. J Pediatr Gastroenterol Nutr. 1993;16:412-418.
69.
Lyoussi B., Crabbe J.Effects of dexamethasone on (Na+ + K+)-ATPase and other parameters related to transepithelial Na+ transport by amphibian renal distal cells (A6) in culture . J Steroid Biochem Mol Biol. 1996;59:333-338.
70.
Smith LM, Ervin MG, Wada N., Ikagami M., Polk DH, Jobe AHAntenatal glucocorticoids alter postnatal preterm lamb renal and cardiovascular responses to intravascular volume expansion. Pediatr Res. 2000;47:622-627.
