Current Hypertension Reports

, Volume 11, Issue 1, pp 56–62 | Cite as

Heme oxygenase and renal disease

Article

Abstract

The cellular content of heme, derived from the breakdown of heme proteins, is regulated via the heme oxygenase (HO) enzyme system. HO catalyzes the rate-limiting step in heme degradation resulting in the formation of iron, carbon monoxide, and biliverdin. Recent studies have focused on the biologic effects of product(s) of this reaction, which have important antioxidant, antiapoptotic, anti-inflammatory, and cytoprotective properties. Two isoforms of the HO enzyme have been described: an inducible isoform (HO-1) and a constitutively expressed isoform (HO-2). Induction of HO-1 occurs as a beneficial response to several injurious stimuli and has been implicated in many clinically relevant disease states including sepsis, hypertension, atherosclerosis, and acute lung and kidney injury. This review focuses on the role of HO-1 in kidney diseases.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Maines MD: The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997, 37:517–554.PubMedCrossRefGoogle Scholar
  2. 2.
    Nath KA: Heme oxygenase-1: a provenance for cytoprotective pathways in the kidney and other tissues. Kidney Int 2006, 70:432–443.PubMedGoogle Scholar
  3. 3.
    Tenhunen R, Marver HS, Schmid R: The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A 1968, 61:748–755.PubMedCrossRefGoogle Scholar
  4. 4.
    Sikorski EM, Hock T, Hill-Kapturczak N, Agarwal A: The story so far: molecular regulation of the heme oxygenase-1 gene in renal injury. Am J Physiol Renal Physiol 2004, 286:F425–F441.PubMedCrossRefGoogle Scholar
  5. 5.
    Alam J, Igarashi K, Immenschuh S, et al.: Regulation of heme oxygenase-1 gene transcription: recent advances and highlights from the International Conference (Uppsala, 2003) on Heme Oxygenase. Antioxid Redox Signal 2004, 6:924–933.PubMedGoogle Scholar
  6. 6.
    Jeney V, Balla J, Yachie A, et al.: Pro-oxidant and cytotoxic effects of circulating heme. Blood 2002, 100:879–887.PubMedCrossRefGoogle Scholar
  7. 7.
    Hill-Kapturczak N, Chang SH, Agarwal A: Heme oxygenase and the kidney. DNA Cell Biol 2002, 21:307–321.PubMedCrossRefGoogle Scholar
  8. 8.
    Balla G, Jacob HS, Balla J, et al.: Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 1992, 267:18148–18153.PubMedGoogle Scholar
  9. 9.
    Inguaggiato P, Gonzalez-Michaca L, Croatt AJ, et al.: Cellular overexpression of heme oxygenase-1 up-regulates p21 and confers resistance to apoptosis. Kidney Int 2001, 60:2181–2191.PubMedCrossRefGoogle Scholar
  10. 10.
    da Silva JL, Zand BA, Yang LM, et al.: Heme oxygenase isoform-specific expression and distribution in the rat kidney. Kidney Int 2001, 59:1448–1457.PubMedCrossRefGoogle Scholar
  11. 11.
    Nath KA, Vercellotti GM, Grande JP, et al.: Heme protein-induced chronic renal inflammation: suppressive effect of induced heme oxygenase-1. Kidney Int 2001, 59:106–117.PubMedCrossRefGoogle Scholar
  12. 12.
    Morimoto K, Ohta K, Yachie A, et al.: Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases. Kidney Int 2001, 60:1858–1866.PubMedCrossRefGoogle Scholar
  13. 13.
    Agarwal A, Nick HS: Renal response to tissue injury: lessons from heme oxygenase-1 gene ablation and expression. J Am Soc Nephrol 2000, 11:965–973.PubMedGoogle Scholar
  14. 14.
    Agarwal A, Kim Y, Matas AJ, et al.: Gas-generating systems in acute renal allograft rejection in the rat. Co-induction of heme oxygenase and nitric oxide synthase. Transplantation 1996, 61:93–98.PubMedCrossRefGoogle Scholar
  15. 15.
    Nath KA, Balla G, Vercellotti GM, et al.: Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. J Clin Invest 1992, 90:267–270.PubMedCrossRefGoogle Scholar
  16. 16.
    Pittock ST, Norby SM, Grande JP, et al.: MCP-1 is up-regulated in unstressed and stressed HO-1 knockout mice: pathophysiologic correlates. Kidney Int 2005, 68:611–622.PubMedCrossRefGoogle Scholar
  17. 17.
    Nath KA, Grande JP, Croatt AJ, et al.: Intracellular targets in heme protein-induced renal injury. Kidney Int 1998, 53:100–111.PubMedCrossRefGoogle Scholar
  18. 18.
    Shimizu H, Takahashi T, Suzuki T, et al.: Protective effect of heme oxygenase induction in ischemic acute renal failure. Crit Care Med 2000, 28:809–817.PubMedCrossRefGoogle Scholar
  19. 19.
    Akagi R, Takahashi T, Sassa S: Cytoprotective effects of heme oxygenase in acute renal failure. Contrib Nephrol 2005, 148:70–85.PubMedCrossRefGoogle Scholar
  20. 20.
    Nakao A, Neto JS, Kanno S, et al.: Protection against ischemia/reperfusion injury in cardiac and renal transplantation with carbon monoxide, biliverdin and both. Am J Transplant 2005, 5:282–291.PubMedCrossRefGoogle Scholar
  21. 21.
    Sung FL, Zhu TY, Au-Yeung KK, et al.: Enhanced MCP-1 expression during ischemia/reperfusion injury is mediated by oxidative stress and NF-kappaB. Kidney Int 2002, 62:1160–1170.PubMedCrossRefGoogle Scholar
  22. 22.
    Tumlin J, Stacul F, Adam A, et al.: Pathophysiology of contrast-induced nephropathy. Am J Cardiol 2006, 98:14K–20K.PubMedCrossRefGoogle Scholar
  23. 23.
    Goodman AI, Olszanecki R, Yang LM, et al.: Heme oxygenase-1 protects against radiocontrast-induced acute kidney injury by regulating anti-apoptotic proteins. Kidney Int 2007, 72:945–953.PubMedCrossRefGoogle Scholar
  24. 24.
    Rezzani R, Rodella L, Buffoli B, et al.: Change in renal heme oxygenase expression in cyclosporine A-induced injury. J Histochem Cytochem 2005, 53:105–112.PubMedCrossRefGoogle Scholar
  25. 25.
    Young BA, Burdmann EA, Johnson RJ, et al.: Cyclosporine A induced arteriolopathy in a rat model of chronic cyclosporine nephropathy. Kidney Int 1995, 48:431–438.PubMedCrossRefGoogle Scholar
  26. 26.
    Shiraishi F, Curtis LM, Truong L, et al.: Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. Am J Physiol Renal Physiol 2000, 278:F726–F736.PubMedGoogle Scholar
  27. 27.
    Tayem Y, Johnson TR, Mann BE, et al.: Protection against cisplatin-induced nephrotoxicity by a carbon monoxidereleasing molecule. Am J Physiol Renal Physiol 2006, 290:F789–F794.PubMedCrossRefGoogle Scholar
  28. 28.
    Boros P, Bromberg JS: New cellular and molecular immune pathways in ischemia/reperfusion injury. Am J Transplant 2006, 6:652–658.PubMedCrossRefGoogle Scholar
  29. 29.
    Katori M, Busuttil RW, Kupiec-Weglinski JW: Heme oxygenase-1 system in organ transplantation. Transplantation 2002, 74:905–912.PubMedCrossRefGoogle Scholar
  30. 30.
    Ollinger R, Kogler P, Biebl M, et al.: Protein levels of heme oxygenase-1 during reperfusion in human kidney transplants with delayed graft function. Clin Transplant 2008, 22:418–423.PubMedGoogle Scholar
  31. 31.
    Baan C, Peeters A, Lemos F, et al.: Fundamental role for HO-1 in the self-protection of renal allografts. Am J Transplant 2004, 4:811–818.PubMedCrossRefGoogle Scholar
  32. 32.
    Courtney AE, McNamee PT, Middleton D, et al.: Association of functional heme oxygenase-1 gene promoter polymorphism with renal transplantation outcomes. Am J Transplant 2007, 7:908–913.PubMedCrossRefGoogle Scholar
  33. 33.
    Martins PN, Kessler H, Jurisch A, et al.: Induction of heme oxygenase-1 in the donor reduces graft immunogenicity. Transplant Proc 2005, 37:384–386.PubMedCrossRefGoogle Scholar
  34. 34.
    Martins PN, Reutzel-Selke A, Jurisch A, et al.: Induction of carbon monoxide in donor animals prior to organ procurement reduces graft immunogenicity and inhibits chronic allograft dysfunction. Transplantation 2006, 82:938–944.PubMedCrossRefGoogle Scholar
  35. 35.
    Johnson RA, Lavesa M, Askari B, et al.: A heme oxygenase product, presumably carbon monoxide, mediates a vasodepressor function in rats. Hypertension 1995, 25:166–169.PubMedGoogle Scholar
  36. 36.
    Liu H, Mount DB, Nasjletti A, Wang W: Carbon monoxide stimulates the apical 70-pS K+ channel of the rat thick ascending limb. J Clin Invest 1999, 103:963–970.PubMedCrossRefGoogle Scholar
  37. 37.
    Rodriguez F, Kemp R, Balazy M, Nasjletti A: Effects of exogenous heme on renal function: role of heme oxygenase and cyclooxygenase. Hypertension 2003, 42:680–684.PubMedCrossRefGoogle Scholar
  38. 38.
    Stec DE, Vera T, McLemore GR, et al.: Heme oxygenase-1 induction does not improve vascular relaxation in angiotensin II hypertensive mice. Am J Hypertens 2008, 21:189–193.PubMedCrossRefGoogle Scholar
  39. 39.
    Vera T, Kelsen S, Stec DE: Kidney-specific induction of heme oxygenase-1 prevents angiotensin II hypertension. Hypertension 2008, 52:660–665.PubMedCrossRefGoogle Scholar
  40. 40.
    Wu CC, Lu KC, Chen JS, et al.: HO-1 induction ameliorates experimental murine membranous nephropathy: antioxidative, anti-apoptotic and immunomodulatory effects. Nephrol Dial Transplant 2008, 23:3082–3090.PubMedCrossRefGoogle Scholar
  41. 41.
    Hruska KA: Treatment of chronic tubulointerstitial disease: a new concept. Kidney Int 2002, 61:1911–1922.PubMedCrossRefGoogle Scholar
  42. 42.
    Moriyama T, Kawada N, Nagatoya K, et al.: Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction. Kidney Int 2001, 59:2095–2103.PubMedGoogle Scholar
  43. 43.
    Kim JH, Yang JI, Jung MH, et al.: Heme oxygenase-1 protects rat kidney from ureteral obstruction via an antiapoptotic pathway. J Am Soc Nephrol 2006, 17:1373–1381.PubMedCrossRefGoogle Scholar
  44. 44.
    Kie JH, Kapturczak MH, Traylor A, et al.: Heme oxygenase-1 deficiency promotes epithelial-mesenchymal transition and renal fibrosis. J Am Soc Nephrol 2008, 19:1681–1691.PubMedCrossRefGoogle Scholar
  45. 45.
    Mishra J, Ma Q, Prada A, et al.: Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003, 14:2534–2543.PubMedCrossRefGoogle Scholar
  46. 46.
    Mishra J, Dent C, Tarabishi R, et al.: Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005, 365:1231–1238.PubMedCrossRefGoogle Scholar
  47. 47.
    Mori K, Lee HT, Rapoport D, et al.: Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 2005, 115:610–621.PubMedGoogle Scholar
  48. 48.
    Lam CW, Getting SJ, Perretti M: In vitro and in vivo induction of heme oxygenase 1 in mouse macrophages following melanocortin receptor activation. J Immunol 2005, 174:2297–2304.PubMedGoogle Scholar
  49. 49.
    Calo LA, Davis PA, Piccoli A, Pessina AC: A role for heme oxygenase-1 in the antioxidant and antiapoptotic effects of erythropoietin: the start of a good news/bad news story? Nephron Physiol 2006, 103:107–111.CrossRefGoogle Scholar
  50. 50.
    Katavetin P, Inagi R, Miyata T, et al.: Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress. Biochem Biophys Res Commun 2007, 359:928–934.PubMedCrossRefGoogle Scholar
  51. 51.
    Lee TS, Chau LY: Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 2002, 8:240–246.PubMedCrossRefGoogle Scholar
  52. 52.
    Tacchini L, Dansi P, Matteucci E, Desiderio MA: Hepatocyte growth factor signalling stimulates hypoxia inducible factor-1 (HIF-1) activity in HepG2 hepatoma cells. Carcinogenesis 2001, 22:1363–1371.PubMedCrossRefGoogle Scholar
  53. 53.
    Lee TS, Chang CC, Zhu Y, Shyy JY: Simvastatin induces heme oxygenase-1: a novel mechanism of vessel protection. Circulation 2004, 110:1296–1302.PubMedCrossRefGoogle Scholar
  54. 54.
    Adin CA, Croker BP, Agarwal A: Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the isolated, perfused rat kidney. Am J Physiol Renal Physiol 2005, 288:F778–F784.PubMedCrossRefGoogle Scholar
  55. 55.
    Vera T, Henegar JR, Drummond HA, et al.: Protective effect of carbon monoxide-releasing compounds in ischemia-induced acute renal failure. J Am Soc Nephrol 2005, 16:950–958.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2009

Authors and Affiliations

  1. 1.Division of Nephrology, THT 647University of Alabama at BirminghamBirminghamUSA

Personalised recommendations