Acta Physiologica Hungarica
Volume/Issue:
Volume 100: Issue 2
Dexamethasone protects from renal ischemia/reperfusion injury: A possible association with SGK-1
Authors: Krisztina Rusai, A. Prokai 1 , C. Juanxing 3 , K. Meszaros 1 , B. Szalay 1 , K. Pásti 1 , V. Müller 2 , U. Heemann 3 , J. Lutz 3 , T. Tulassay 1 , and A. Szabo 1
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  • 1 Department of Pediatrics, and Nephrology Research Laboratory of the Hungarian Academy of Sciences Budapest Hungary
  • 2 Semmelweis University Department of Pulmology Budapest Hungary
  • 3 Technical University Department of Nephrology Munich Germany
  • 4 Semmelweis University Department of Pediatrics Bókay utca 53-54 H-1083 Budapest Hungary
DOI:
https://doi.org/10.1556/APhysiol.100.2013.001
Page Count:
173–185
Publication Date:
01 Jun 2013
Online Publication Date:
23 Mar 2013
Article Category:
Research Article
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Previous experimental data suggest that steroids might have protective effects during hypoxic/ischemic injury of various organs. In this study, the association between dexamethason (Dexa) treatment and the anti-apoptotic SGK-1 was tested in ischemic renal injury. In vitro, HK-2 cells were exposed to 24 h hypoxia, and the effect of Dexa incubation on SGK-1 expression / activation and on cell death was studied. In an in vivo rat model of unilateral renal IR, animals were treated with Dexa, and serum renal function parameters, tissue injury and SGK-1 expression and localization were examined after different reperfusion times (2 h, 4 h and 24 h). Dexa at a dose of 2 mg/L exerted a protective effect on cell survival assessed by LDH release and vital staining paralleled by marked up-regulation of SGK-1. In rats, 2 mg/kg Dexa treatment 24 h prior to ischemia resulted in less severe tissue injury and ameliorated urea nitrogen levels 24 h after reperfusion. Furthermore, SGK-1 expression and phosphorylation were higher in Dexa animals demonstrated by Western blot and immunofluorescence technique. Our results provide novel data on the signalling mechanism of Dexa under hypoxia / ischemia and further support that Dexa emerges as an attractive pharmacological agent for the prevention of ischemic injury.

  • Attarzadeh-Yazdi G, Shipston MJ, Antoni FA: Dex-ras1 and serum- and glucocorticoid-inducible protein kinase 1: regulation of expression by dexamethasone in HEK293 cells. Neurochem. Res. 33, 609–613 (2008)

    Antoni F.A. , 'Dex-ras1 and serum- and glucocorticoid-inducible protein kinase 1: regulation of expression by dexamethasone in HEK293 cells ' (2008 ) 33 Neurochem. Res : 609 -613.

    • Search Google Scholar

  • Baker RC, Armstrong MA, Young IS, McClean E, O’Rourke D, Campbell FC, D’sa AA, McBride WT: Methylprednisolone increases urinary nitrate concentrations and reduces subclinical renal injury during infrarenal aortic ischemia reperfusion. Ann. Surg. 244, 821–826 (2006)

    McBride W.T. , 'Methylprednisolone increases urinary nitrate concentrations and reduces subclinical renal injury during infrarenal aortic ischemia reperfusion ' (2006 ) 244 Ann. Surg : 821 -826.

    • Search Google Scholar

  • Barzilai D, Plavnick J, Hazani A, Einath R, Kleinhaus N, Kanter Y: Use of hydrocortisone in the treatment of acute myocardial infarction. Summary of a clinical trial in 446 patients. Chest 61, 488–491 (1972)

    Kanter Y. , 'Use of hydrocortisone in the treatment of acute myocardial infarction. Summary of a clinical trial in 446 patients ' (1972 ) 61 Chest : 488 -491.

    • Search Google Scholar

  • Brennan FE, Fuller PJ: Rapid upregulation of serum and glucocorticoid-regulated kinase (sgk) gene expression by corticosteroids in vivo. Mol. Cell. Endocrinol. 166, 129–136 (2000)

    Fuller P.J. , 'Rapid upregulation of serum and glucocorticoid-regulated kinase (sgk) gene expression by corticosteroids in vivo ' (2000 ) 166 Mol. Cell. Endocrinol : 129 -136.

    • Search Google Scholar

  • Brunet A, Park J, Tran H, Hu LS, Hemmings BA, Greenberg ME: Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol. Cell Biol. 21, 952–965 (2001)

    Greenberg M.E. , 'Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a) ' (2001 ) 21 Mol. Cell Biol : 952 -965.

    • Search Google Scholar

  • Chiang CH, Wu CP, Perng WC, Yan HC, Yu CP: Dexamethasone and pentastarch produce additive attenuation of ischaemia/reperfusion lung injury. Clin. Sci. (Lond.) 99, 413–419 (2000)

    Yu C.P. , 'Dexamethasone and pentastarch produce additive attenuation of ischaemia/reperfusion lung injury ' (2000 ) 99 Clin. Sci. (Lond.) : 413 -419.

    • Search Google Scholar

  • Fan WJ, Genade S, Genis A, Huisamen B, Lochner A: Dexamethasone-induced cardioprotection: a role for the phosphatase MKP-1? Life Sci. 84, 838–846 (2009)

    Lochner A. , 'Dexamethasone-induced cardioprotection: a role for the phosphatase MKP-1? ' (2009 ) 84 Life Sci. : 838 -846.

    • Search Google Scholar

  • Feng Y, Wang Y, Xiong J, Lang F: Expression and significance of serum and glucocorticoid inducible kinase-1 in kidney damage following L-NAME induced hypertension. Kidney Blood Pressure Res. 29, 94–99 (2006)

    Lang F. , 'Expression and significance of serum and glucocorticoid inducible kinase-1 in kidney damage following L-NAME induced hypertension ' (2006 ) 29 Kidney Blood Pressure Res : 94 -99.

    • Search Google Scholar

  • de Fijter JW: Rejection and function and chronic allograft dysfunction. Kidney Int. 119, 38–41 (2010)

    Fijter J.W. , 'Rejection and function and chronic allograft dysfunction ' (2010 ) 119 Kidney Int : 38 -41.

    • Search Google Scholar

  • Feng Y, Rhodes PG, Bhatt AJ: Dexamethasone pre-treatment protects brain against hypoxic-ischemic injury partially through up-regulation of vascular endothelial growth factor A in neonatal rats. Neuroscience 179, 223–232 (2011)

    Bhatt A.J. , 'Dexamethasone pre-treatment protects brain against hypoxic-ischemic injury partially through up-regulation of vascular endothelial growth factor A in neonatal rats ' (2011 ) 179 Neuroscience : 223 -232.

    • Search Google Scholar

  • Hafezi-Moghadam A, Simoncini T, Yang Z, Limbourg FP, Plumier JC, Rebsamen MC, Hsieh CM, Chui DS, Thomas KL, Prorock AJ, Laubach VE, Moskowitz MA, French BA, Ley K, Liao JK: Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nat. Med. 8, 473–479 (2002)

    Liao J.K. , 'Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase ' (2002 ) 8 Nat. Med : 473 -479.

    • Search Google Scholar

  • Islam MK, Rahman AT, Arif NU, Bhuiyan AK, Islam MM, Khan SA, Rahman AM: Modified perfusion fluid for renal transplantation in developing countries: our initial experience. Transplant. Proc. 42, 1531–1535 (2010)

    Rahman A.M. , 'Modified perfusion fluid for renal transplantation in developing countries: our initial experience ' (2010 ) 42 Transplant. Proc : 1531 -1535.

    • Search Google Scholar

  • Johns DG, Ao Z, Willette RN, Macphee CH, Douglas SA: Role of p38 MAP kinase in postcapillary venule leukocyte adhesion induced by ischemia/reperfusion injury. Pharmacol. Res. 51, 463–471 (2005)

    Douglas S.A. , 'Role of p38 MAP kinase in postcapillary venule leukocyte adhesion induced by ischemia/reperfusion injury ' (2005 ) 51 Pharmacol. Res : 463 -471.

    • Search Google Scholar

  • Kumar S, Allen DA, Kieswich JE, Patel NS, Harwood S, Mazzon E, Cuzzocrea S, Raftery MJ, Thiemermann C, Yaqoob MM: Dexamethasone ameliorates renal ischemia-reperfusion injury. J. Am. Soc. Nephrol. 20, 2412–2425 (2009)

    Yaqoob M.M. , 'Dexamethasone ameliorates renal ischemia-reperfusion injury ' (2009 ) 20 J. Am. Soc. Nephrol : 2412 -2425.

    • Search Google Scholar

  • Lang F, Böhmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V: (Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms. Physiol. Rev. 86, 1151–1178 (2006)

    Vallon V. , '(Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms ' (2006 ) 86 Physiol. Rev : 1151 -1178.

    • Search Google Scholar

  • Limbourg FP, Huang Z, Plumier JC, Simoncini T, Fujioka M, Tuckermann J, Schutz G, Moskowitz MA, Liao JK: Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids. J. Clin. Invest. 110, 1729–1738 (2002)

    Liao J.K. , 'Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids ' (2002 ) 110 J. Clin. Invest : 1729 -1738.

    • Search Google Scholar

  • Leong ML, Maiyar AC, Kim B, O’Keeffe BA, Firestone G: Expression of the serum- and glucocorticoidinducible protein kinase, Sgk, is a cell survival response to multiple types of environmental stress stimuli in mammary epithelial cells. J. Biol. Chem. 278, 5871–5882 (2003)

    Firestone G. , 'Expression of the serum- and glucocorticoidinducible protein kinase, Sgk, is a cell survival response to multiple types of environmental stress stimuli in mammary epithelial cells ' (2003 ) 278 J. Biol. Chem : 5871 -5882.

    • Search Google Scholar

  • Morariu AM, Loef BG, Aarts LP, Rietman GW, Rakhorst G, van Oeveren W, Epema AH: Dexamethasone: benefit and prejudice for patients undergoing on-pump coronary artery bypass grafting: a study on myocardial, pulmonary, renal, intestinal, and hepatic injury. Chest 128, 2677–2687 (2005)

    Epema A.H. , 'Dexamethasone: benefit and prejudice for patients undergoing on-pump coronary artery bypass grafting: a study on myocardial, pulmonary, renal, intestinal, and hepatic injury ' (2005 ) 128 Chest : 2677 -2687.

    • Search Google Scholar

  • Mikosz CA, Brickley DR, Sharkey MS, Moran TW, Conzen SD: Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1. J. Biol. Chem. 276, 16649–16654 (2001)

    Conzen S.D. , 'Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1 ' (2001 ) 276 J. Biol. Chem : 16649 -16654.

    • Search Google Scholar

  • Palm F, Nordquist L: Renal tubulointerstitial hypoxia: cause and consequence of kidney dysfunction. Clin. Exp. Pharmacol. Physiol. 38, 424–430 (2011)

    Nordquist L. , 'Renal tubulointerstitial hypoxia: cause and consequence of kidney dysfunction ' (2011 ) 38 Clin. Exp. Pharmacol. Physiol : 424 -430.

    • Search Google Scholar

  • Pascual J, Zamora J, Galeano C, Royuela A, Quereda C: Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst. Rev. 2009 Jan 21; (1): CD005632.

  • Ribichini F, Tomai F, Paloscia L, Di Sciascio G, Carosio G, Romano M, Verna E, Galli M, Tamburino C, De Cesare N, Pirisi R, Piscione F, Lanteri G, Ferrero V, Vassanelli C: DESIRE investigators. Steroid-eluting stents in patients with acute coronary syndrome: the dexamethasone eluting stent Italian registry. Heart 93, 598–600 (2007)

    Vassanelli C. , 'DESIRE investigators. Steroid-eluting stents in patients with acute coronary syndrome: the dexamethasone eluting stent Italian registry ' (2007 ) 93 Heart : 598 -600.

    • Search Google Scholar

  • Rusai K, Fekete A, Szebeni B, Vannay A, Bokodi G, Müller V, Viklicky O, Bloudickova S, Rajnoch J, Heemann U, Reusz G, Szabó A, Tulassay T, Szabó AJ: Effect of inhibition of neuronal nitric oxide synthase and L-arginine supplementation on renal ischaemia-reperfusion injury and the renal nitric oxide system. Clin. Exp. Pharmacol. Physiol. 35, 1183–1189 (2008)

    Szabó A.J. , 'Effect of inhibition of neuronal nitric oxide synthase and L-arginine supplementation on renal ischaemia-reperfusion injury and the renal nitric oxide system ' (2008 ) 35 Clin. Exp. Pharmacol. Physiol : 1183 -1189.

    • Search Google Scholar

  • Rusai K, Wagner B, Roos M, Schmaderer C, Strobl M, Boini KM, Grenz A, Kuhl D, Heemann U, Lang F, Lutz J: The serum and glucocorticoid-regulated kinase 1 in hypoxic renal injury. Cell. Physiol. Biochem. 24, 577–584 (2009)

    Lutz J. , 'The serum and glucocorticoid-regulated kinase 1 in hypoxic renal injury ' (2009 ) 24 Cell. Physiol. Biochem : 577 -584.

    • Search Google Scholar

  • Rusai K, Prókai A, Szebeni B, Fekete A, Treszl A, Vannay A, Müller V, Reusz G, Heemann U, Lutz J, Tulassay T, Szabó AJ: Role of serum and glucocorticoid-regulated kinase-1 in the protective effects of erythropoietin during renal ischemia/reperfusion injury. Biochem. Pharmacol. 79, 1173–1181 (2010)

    Szabó A.J. , 'Role of serum and glucocorticoid-regulated kinase-1 in the protective effects of erythropoietin during renal ischemia/reperfusion injury ' (2010 ) 79 Biochem. Pharmacol : 1173 -1181.

    • Search Google Scholar

  • Rusai K, Prókai A, Szebeni B, Meszaros K, Fekete A, Szalay B, Vannay A, Degrell P, Müller V, Tulassay T, Szabó AJ: Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury. Cell. Physiol. Biochem. 27, 727–738 (2011)

    Szabó A.J. , 'Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury ' (2011 ) 27 Cell. Physiol. Biochem : 727 -738.

    • Search Google Scholar

  • Sasson R, Amsterdam A: Pleiotropic anti-apoptotic activity of glucocorticoids in ovarian follicular cells. Biochem. Pharmacol. 66, 1393–1401 (2003)

    Amsterdam A. , 'Pleiotropic anti-apoptotic activity of glucocorticoids in ovarian follicular cells ' (2003 ) 66 Biochem. Pharmacol : 1393 -1401.

    • Search Google Scholar

  • Sharfuddin AA, Molitoris BA: Pathophysiology of ischemic acute kidney injury. Nat. Rev. Nephrol. 7, 189–200 (2011)

    Molitoris B.A. , 'Pathophysiology of ischemic acute kidney injury ' (2011 ) 7 Nat. Rev. Nephrol : 189 -200.

    • Search Google Scholar

  • Szabo A, Heemann U: Ischemia/reperfusion and chronic allograft rejection. Transplant. Proc. 30, 4281–4284 (1998)

    Heemann U. , 'Ischemia/reperfusion and chronic allograft rejection ' (1998 ) 30 Transplant. Proc : 4281 -4284.

    • Search Google Scholar

  • Takahira R, Yonemura K, Fujise Y, Hishida A: Dexamethasone attenuates neutrophil infiltration in the rat kidney in ischemia/reperfusion injury: the possible role of nitroxyl. Free Radic. Biol. Med. 31, 809–815 (2001)

    Hishida A. , 'Dexamethasone attenuates neutrophil infiltration in the rat kidney in ischemia/reperfusion injury: the possible role of nitroxyl ' (2001 ) 31 Free Radic. Biol. Med : 809 -815.

    • Search Google Scholar

  • Tokudome S, Sano M, Shinmura K, Matsuhashi T, Morizane S, Moriyama H, Tamaki K, Hayashida K, Nakanishi H, Yoshikawa N, Shimizu N, Endo J, Katayama T, Murata M, Yuasa S, Kaneda R, Tomita K, Eguchi N, Urade Y, Asano K, Utsunomiya Y, Suzuki T, Taguchi R, Tanaka H, Fukuda K: Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase-derived PGD2 biosynthesis J. Clin. Invest. 119, 1477–1488 (2009)

    Fukuda K. , 'Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase-derived PGD2 biosynthesis J ' (2009 ) 119 Clin. Invest : 1477 -1488.

    • Search Google Scholar

  • Ullrich S, Berchtold S, Ranta F, Seebohm G, Henke G, Lupescu A, Mack AF, Chao CM, Su J, Nitschke R, Alexander D, Friedrich B, Wulff P, Kuhl D, Lang F: Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates glucocorticoid-induced inhibition of insulin secretion. Diabetes 54, 1090–1099 (2005)

    Lang F. , 'Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates glucocorticoid-induced inhibition of insulin secretion ' (2005 ) 54 Diabetes : 1090 -1099.

    • Search Google Scholar

  • Varga E, Nagy N, Lazar J, Czifra G, Bak I, Biro T, Tosaki A: Inhibition of ischemia/reperfusion-induced damage by dexamethasone in isolated working rat hearts: the role of cytochrome c release. Life Sci. 75, 2411–2423 (2004)

    Tosaki A. , 'Inhibition of ischemia/reperfusion-induced damage by dexamethasone in isolated working rat hearts: the role of cytochrome c release ' (2004 ) 75 Life Sci : 2411 -2423.

    • Search Google Scholar

  • Wada T, Pippin JW, Marshall CB, Griffin SV, Shankland SJ: Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and Bcl-2-related family proteins. J. Am. Soc. Nephrol. 16, 2615–2625 (2005)

    Shankland S.J. , 'Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and Bcl-2-related family proteins ' (2005 ) 16 J. Am. Soc. Nephrol : 2615 -2625.

    • Search Google Scholar

  • Wu W, Zou M, Brickley DR, Pew T, Conzen SD: Glucocorticoid receptor activation signals through forkhead transcription factor 3a in breast cancer cells. Mol. Endocrinol. 20, 2304–2314 (2006)

    Conzen S.D. , 'Glucocorticoid receptor activation signals through forkhead transcription factor 3a in breast cancer cells ' (2006 ) 20 Mol. Endocrinol : 2304 -2314.

    • Search Google Scholar

  • Xu B, Strom J, Chen QM: Dexamethasone induces transcriptional activation of Bcl-xL gene and inhibits cardiac injury by myocardial ischemia. Eur. J. Pharmacol. 668, 194–200 (2011)

    Chen Q.M. , 'Dexamethasone induces transcriptional activation of Bcl-xL gene and inhibits cardiac injury by myocardial ischemia ' (2011 ) 668 Eur. J. Pharmacol : 194 -200.

    • Search Google Scholar

  • You H, Jang Y, You T, Okada H, Liepa J, Wakeham A, Zaugg K, Mak TW: p53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1. Proc. Natl Acad. Sci. USA 101, 14057–14062 (2004)

    Mak T.W. , 'p53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1 ' (2004 ) 101 Proc. Natl Acad. Sci. USA : 14057 -14062.

    • Search Google Scholar

  • Zhang L, Cui R, Cheng X, Du J: Antiapoptotic effect of serum and glucocorticoid-inducible protein kinase is mediated by novel mechanism activating IκB kinase. Cancer Res. 65, 457–464 (2005)

    Du J. , 'Antiapoptotic effect of serum and glucocorticoid-inducible protein kinase is mediated by novel mechanism activating IκB kinase ' (2005 ) 65 Cancer Res : 457 -464.

    • Search Google Scholar
Cover Acta Physiologica Hungarica
Acta Physiologica Hungarica
Print ISSN:
0231-424X
Online ISSN:
1588-2683
Keywords:
dexamethasone; mechanism; protection; renal ischemia-reperfusion

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