Spironolactone, but not enalapril, potentiates hypoxia-inducible factor-1alpha and Ets-1 expression in newborn rat kidney

• Autorzy: Yim H. E. , Kim J.H. , Yoo K.H. , Bae I.S. , Jang G.Y. , Hong Y.S. , Lee J.W.
• Języki publikacji: EN

Abstrakty

EN

Hypoxia is regarded as an important physiological factor that controls nephrogenesis. We investigated whether the renin-angiotensin-aldosterone system (RAAS) affects hypoxia-related target genes in developing kidneys. Newborn rat pups were treated with enalapril (30 mg/kg/d) or spironolactone (200 mg/kg/d) for 7 days. Tissue hypoxia was assessed by the uptake of a hypoxyprobe-1, pimonidazole (200 mg/kg), and the expression of hypoxia-responsive genes. In the enalapril group, hypoxia-inducible factor (HIF)-1, HIF-2, and Ets-1 protein expression were not changed, compared to the control group. In the spironolactone group, HIF-1 and Ets-1 protein expression were significantly increased by immunoblots and immunohistochemistry, whereas HIF-2 protein expression was not changed, compared to the control group. In the enalapril group, the immunoactivity of pimonidazole was not significantly different from that of the controls. However, in the spironolactone group, pimonidazole staining demonstrated that the cortex and medulla underwent severe hypoxia. In summary, our data showed that aldosterone inhibition in the developing kidney augmented the hypoxic responses, and up-regulated the expression of key mediators of hypoxia including HIF-1 and Ets-1. Angiotensin II inhibition did not affect hypoxia-related alterations in the developing kidney. The components of RAAS may differentially modulate renal hypoxia and its related target genes in the developing rat kidney.

Słowa kluczowe

EN

spironolactone; enalapril; hypoxia-inducible factor-1alpha; Ets-1 protein expression; renin-angiotensin-aldosterone system; angiotensin; aldosterone; hypoxia; kidney; angiotensin converting enzyme; rat

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 1
• Opis fizyczny: p.73-81,fig.,ref.

Twórcy

autor

Yim H. E.

• Korea University Medical Center 80, Guro-Dong, Guro-Gu, Seoul, 152-703, Korea

autor

Kim J.H.

autor

Yoo K.H.

autor

Bae I.S.

autor

Jang G.Y.

autor

Hong Y.S.

autor

Lee J.W.

Bibliografia

• Ishizawa K, Izawa Y, Ito H, et al. Aldosterone stimulates vascular smooth muscle cell proliferation via big mitogen-activated protein kinase 1 activation. Hypertension 2005; 46: 1046-1052.
• Choi BM, Yoo KH, Bae IS, et al. Angiotensin-converting enzyme inhibition modulates mitogen-activated protein kinase family expressions in the neonatal rat kidney. Pediatr Res 2005; 57: 115-123.
• HE Yim, KH Yoo, IS Bae, GY Jang, YS Hong, JW Lee. Aldosterone regulates cellular turnover and mitogen-activated protein kinase family expression in the neonatal rat kidney. J Cell Physiol 2009; 219: 724-733.
• Haddad JJ. Hypoxia and the regulation of mitogen-activated protein kinases: gene transcription and the assessment of potential pharmacologic therapeutic interventions. Int Immnunopharmacol 2004; 4: 1249-1285.
• Freeburg PB, Abrahamson DR. Hypoxia-inducible factors and kidney vascular development. J Am Soc Nephrol 2003; 14: 2723-2730.
• Nava S, Bocconi L, Zuliani G, Kustermann A, Nicolini U. Aspects of fetal physiology from 18 to 37 weeks' gestation as assessed by blood sampling. Obstet Gynecol 1996; 87: 975-980.
• Freeburg PB, Robert B, St John PL, Abrahamson DR. Podocyte expression of hypoxia-inducible factor (HIF)-1 and HIF-2 during glomerular development. J Am Soc Nephrol 2003; 14: 927-938.
• Lee YM, Jeong CH, Koo SY, et al. Determination of hypoxic region by hypoxia marker in developing mouse embryos in vivo: A possible signal for vessel development. Dev Dyn 2001; 220: 175-186.
• Bernhardt WM, Schmitt R, Rosenberger C, et al. Expression of hypoxia-inducible transcription factors in developing human and rat kidneys. Kidney Int 2006; 69: 114-122.
• Jaakkola P, Mole DR, Tian YM, et al. Targeting of HIF-1 to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 2001; 292: 468-472.
• Iyer NV, Kotch LE, Agani F, et al. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1. Genes Dev 1998; 12: 149-162.
• Maltepe E, Schmidt JV, Baunoch D, Bradford CA, Simon MC. Abnormal angiogenesis and responses to glucose deprivation in mice lacking the protein ARNT. Nature 1997; 386: 403-407.
• Peng J, Zhang L, Drysdale L, Fong GH. The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an important role in vascular remodeling. Proc Natl Acad Sci USA 2000; 97: 8386-8391.
• Oikawa M, Abe M, Kurosawa H, Hida W, Shirato K, Sato Y. Hypoxia induces transcription factor ETS-1 via the activity of hypoxia-inducible factor-1. Biochem Biophys Res Commun 2002; 89: 39-43.
• Tanaka H, Terada Y, Kobayashi T, et al. Expression and function of Ets-1 during experimental acute renal failure in rats. J Am Soc Nephrol 2004; 15: 3083-3092.
• Sharrocks AD. The ET: S-domain transcription factor family. Nat Rev Mol Cell Biol 2001; 2: 827-837.
• Lelievre E, Lionneton F, Soncin F, Vandenbunder B. The Ets family contains transcriptional activators and repressors involved in angiogenesis. Int J Biochem Cell Biol 2001; 33: 391-407.
• Kola I, Brookes S, Green AR, et al. The Ets1 transcription factor is widely expressed during murine embryo development and is associated with mesodermal cells involved in morphogenetic processes such as organ formation. Proc Natl Acad Sci USA 1993; 90: 7588-7592.
• Nigam SK, Aperia AC, Brenner BM. Development and maturation of the kidney. In: The Kidney, Brenner BM, Rector FC (eds). Philadelphia, WB Saunders Company, 1996, pp. 72-98.
• Bauer JH. Age-related changes in the renin-aldosterone system. Physiological effects and clinical implications. Drugs Aging 1993; 3: 238-245.
• Schofield CJ, Ratcliffe PJ. Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 2004; 5: 343-354.
• Gomez RA, Lynch KR, Chevalier RL, et al. Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition. Am J Physiol 1988; 254: F900-F906.
• Gallego M, Espina L, Vegas L, Echevarria E, Iriarte MM, Casis O. Spironolactone and captopril attenuates isoproterenol-induced cardiac remodeling in rats. Pharmacol Res 2001; 44: 311-316.
• Tisdale EJ. Glyceraldehyde-3-phosphate dehydrogenase is required for vesicular transport in the early secretory pathway. J Biol Chem 2001; 276: 2480-2486.
• Arteel GE, Thurman RG, Yates JM, Raleigh JA. Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver. Br J Cancer 1995; 72: 889-895.
• Zou AP, Cowley AW Jr. Reactive oxygen species and molecular regulation of renal oxygenation. Acta Physiol Scand 2003; 179: 233-241.
• Epstein FH. Oxygen and renal metabolism. Kidney Int 1997; 51: 381-385.
• Cederberg A, Hulander M, Carlsson P, Enerback S. The kidney-expressed winged helix transcription factor FREAC-4 is regulated by Ets-1. A possible role in kidney development. J Biol Chem 1999; 274: 165-169.
• Canessa CM, Schild L, Buell G, et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature 1994; 367: 463-467.
• Berger S, Bleich M, Schmid W, et al. Mineralocorticoid receptor knockout mice: pathophysiology of Na+ metabolism. Proc Natl Acad Sci USA 1998; 95: 9424-9429.
• O'Connor PM. Renal oxygen delivery: matching delivery to metabolic demand. Clin Exp Pharmacol Physiol 2006; 33: 961-967.
• Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int 2003; 63: 1791-1800.
• Chrysostomou A, Becker G. Spironolactone in addition to ACE inhibition to reduce proteinuria in patients with chronic renal disease. N Engl J Med 2001; 20: 925-926.
• Patni H, Mathew JT, Luan L, Franki N, Chander PN, Singhal PC. Aldosterone promotes proximal tubular cell apoptosis: role of oxidative stress. Am J Physiol Renal Physiol 2007; 293: F1065-F1071.
• Iwazu Y, Muto S, Fujisawa G, et al. Spironolactone suppresses peritubular capillary loss and prevents deoxycorticosterone acetate/salt-induced tubulointerstitial fibrosis. Hypertension 2008; 51: 749-754.
• Bridgham JT, Carroll SM, Thornton JW. Evolution of hormone-receptor complexity by molecular exploitation. Science 2006; 7: 97-101.
• Rosenberger C, Griethe W, Gruber G, et al. Cellular responses to hypoxia after renal segmental infarction. Kidney Int 2003; 64: 874-886.
• Rosenberger C, Mandriota S, Jurgensen JS, et al. Expression of hypoxia-inducible factor-1alpha and -2alpha in hypoxic and ischemic rat kidneys. J Am Soc Nephrol 2002; 13: 1721-1732.
• Urata H, Kinoshita A, Misono KS, Bumpus FM, Husain A. Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem 1990; 265: 22348-22357.
• Urata H, Strobel F, Ganten D. Widespread tissue distribution of human chymase. J Hypertens 1994; 12: S17-S22.
• Cristovam PC, Arnoni CP, de Andrade MC, et al. ACE-dependent and chymase-dependent angiotensin II generation in normal and glucose-stimulated human mesangial cells. Exp Biol Med 2008; 233: 1035-1043.
• Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev 2007; 59: 251-287.
• Gainer JV, Morrow JD, Loveland A, King DJ, Brown NJ. Effect of bradykinin-receptor blockade on the response to angiotensin-converting-enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med 1998; 339: 1285-1292.
• Campbell DJ, Kladis A, Duncan AM. Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides. Hypertension 1994; 23: 439-449.
• Jaspard E, Wei L, Alhenc-Gelas F. Differences in the properties and enzymatic specificities of the two active sites of angiotensin I-converting enzyme (kininase II). Studies with bradykinin and other natural peptides. J Biol Chem 1993; 268: 9496-9503.