Skip to main content

Advertisement

SpringerLink
Log in

Identification of a novel aldose reductase-like gene upregulated in the failing heart of cardiomyopathic hamster

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Cardiomyopathy (CM) is degenerative disease of myocardium which leads to severe cardiac failure. Although many causative genes for CM have been identified, molecular pathogenesis of CM is not fully understood. In this study, we searched for a novel pathway recruited in the development of CM by using BIO14.6 hamster as an animal model for human CM. We screened upregulated genes in the left ventricle by differential display technique and searched for a gene which had never been linked to CM. We identified a novel gene overexpressed in BIO14.6 hamster ventricles, which was considered to be a new member of aldo–keto reductase (AKR) superfamily. The cloned cDNA encoded a 316 amino acid polypeptide with calculated molecular mass of 35,804, which showed high amino acid sequence similarities to aldose reductase and its relative: 69.6% to AKR1B1 (human aldose reductase), 68.4% to AKR1B3 (mouse aldose reductase), and 85.8% to AKR1B7 (mouse vas deferens protein). The upregulation of this aldose reductase-like gene in BIO14.6 hamster ventricles (6.3 ± 0.8-fold) seemed to be influenced by the overexpression of activator protein-1 present there. With the fact that AKR1B1, AKR1B3, and AKR1B7 have synthetic activities of prostaglandin F2α, the aldose reductase-like protein could cause cardiac hypertrophy through production of prostaglandin F2α whose precursor and receptor were abundant in BIO14.6 hamster ventricles. Aldose reductase and its related proteins would give a new clue to dissect the pathogenesis of CM including oxidative stress and cardiac hypertrophy, and to develop a new drug for the treatment of CM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Braunwald E, Bristow MR (2000) Congestive heart failure: fifty years of progress. Circulation 102:IV14–IV23

    PubMed  CAS  Google Scholar 

  2. Ross J Jr (2002) Dilated cardiomyopathy: concepts derived from gene deficient and transgenic animal models. Circ J 66:219–224

    Article  PubMed  CAS  Google Scholar 

  3. Struber M, Meyer AL, Malehsa D, Kugler C, Simon AR, Haverich A (2009) The current status of heart transplantation and the development of “artificial heart systems”. Dtsch Arztebl Int 106:471–477

    PubMed  Google Scholar 

  4. McNally E, Allikian M, Wheeler MT, Mislow JM, Heydemann A (2003) Cytoskeletal defects in cardiomyopathy. J Mol Cell Cardiol 35:231–241

    Article  PubMed  CAS  Google Scholar 

  5. Paul M, Zumhagen S, Stallmeyer B, Koopmann M, Spieker T, Schulze-Bahr E (2009) Genes causing inherited forms of cardiomyopathies. A current compendium. Herz 34:98–109

    Article  PubMed  Google Scholar 

  6. Lyon AR, Sato M, Hajjar RJ, Samulski RJ, Harding SE (2008) Gene therapy: targeting the myocardium. Heart 94:89–99

    Article  PubMed  CAS  Google Scholar 

  7. Gersh BJ, Simari RD, Behfar A, Terzic CM, Terzic A (2009) Cardiac cell repair therapy: a clinical perspective. Mayo Clin Proc 84:876–892

    Article  PubMed  CAS  Google Scholar 

  8. Towbin JA, Bowles NE (2006) Dilated cardiomyopathy: a tale of cytoskeletal proteins and beyond. J Cardiovasc Electrophysiol 17:919–926

    Article  PubMed  Google Scholar 

  9. Sakamoto A (2004) Electrical and ionic abnormalities in the heart of cardiomyopathic hamsters: in quest of a new paradigm for cardiac failure and lethal arrhythmia. Mol Cell Biochem 259:183–187

    Article  PubMed  CAS  Google Scholar 

  10. Yasumura Y, Takemura K, Sakamoto A, Kitakaze M, Miyatake K (2003) Changes in myocardial gene expression associated with beta-blocker therapy in patients with chronic heart failure. J Card Fail 9:469–474

    Article  PubMed  CAS  Google Scholar 

  11. Shigeyama J, Yasumura Y, Sakamoto A, Ishida Y, Fukutomi T, Itoh M, Miyatake K, Kitakaze M (2005) Increased gene expression of collagen types I and III is inhibited by beta-receptor blockade in patients with dilated cardiomyopathy. Eur Heart J 26:2698–2705

    Article  PubMed  CAS  Google Scholar 

  12. Inoue A, Yamashina S, Yamazaki J (2003) The effect of beta-blocker on hamster model bio 53.58 with dilated cardiomyopathy determined using 123I-MIBG myocardial scintigraphy. Ann Nucl Med 17:677–683

    Article  PubMed  CAS  Google Scholar 

  13. Nigro V, Okazaki Y, Belsito A, Piluso G, Matsuda Y, Politano L, Nigro G, Ventura C, Abbondanza C, Molinari AM, Acampora D, Nishimura M, Hayashizaki Y, Puca GA (1997) Identification of the Syrian hamster cardiomyopathy gene. Hum Mol Genet 6:601–607

    Article  PubMed  CAS  Google Scholar 

  14. Sakamoto A, Ono K, Abe M, Jasmin G, Eki T, Murakami Y, Masaki T, Toyo-oka T, Hanaoka F (1997) Both hypertrophic and dilated cardiomyopathies are caused by mutation of the same gene, delta-sarcoglycan, in hamster: an animal model of disrupted dystrophin-associated glycoprotein complex. Proc Natl Acad Sci USA 94:13873–13878

    Article  PubMed  CAS  Google Scholar 

  15. Sakamoto A, Abe M, Masaki T (1999) Delineation of genomic deletion in cardiomyopathic hamster. FEBS Lett 447:124–128

    Article  PubMed  CAS  Google Scholar 

  16. Blake DJ, Weir A, Newey SE, Davies KE (2002) Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 82:291–329

    PubMed  CAS  Google Scholar 

  17. Tsubata S, Bowles KR, Vatta M, Zintz C, Titus J, Muhonen L, Bowles NE, Towbin JA (2000) Mutations in the human delta-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. J Clin Invest 106:655–662

    Article  PubMed  CAS  Google Scholar 

  18. Sakamoto A (2003) Molecular pathogenesis of severe cardiomyopathy in the TO-2 hamster. Exp Clin Cardiol 8:143–146

    PubMed  CAS  Google Scholar 

  19. Matsuhisa S, Otani H, Okazaki T, Yamashita K, Akita Y, Sato D, Moriguchi A, Iwasaka T (2008) N-acetylcysteine abolishes the protective effect of losartan against left ventricular remodeling in cardiomyopathy hamster. Antioxid Redox Signal 10:1999–2008

    Article  PubMed  CAS  Google Scholar 

  20. Morozova O, Hirst M, Marra MA (2009) Applications of new sequencing technologies for transcriptome analysis. Annu Rev Genomics Hum Genet 10:135–151

    Article  PubMed  CAS  Google Scholar 

  21. Sakamoto A, Ishibashi-Ueda H, Sugamoto Y, Higashikata T, Miyamoto S, Kawashiri MA, Yagi K, Konno T, Hayashi K, Fujino N, Ino H, Takeda Y, Yamagishi M (2008) Expression and function of ephrin-b1 and its cognate receptor EphB2 in human atherosclerosis: from an aspect of chemotaxis. Clin Sci (Lond) 114:643–650

    Article  CAS  Google Scholar 

  22. Hyndman D, Bauman DR, Heredia VV, Penning TM (2003) The aldo–keto reductase superfamily homepage. Chem Biol Interact 143–144:621–631

    Article  PubMed  Google Scholar 

  23. Penning TM, Drury JE (2007) Human aldo–keto reductases: function, gene regulation, and single nucleotide polymorphisms. Arch Biochem Biophys 464:241–250

    Article  PubMed  CAS  Google Scholar 

  24. Sakamoto A, Yanagisawa M, Sakurai T, Takuwa Y, Yanagisawa H, Masaki T (1991) Cloning and functional expression of human cDNA for the ETB endothelin receptor. Biochem Biophys Res Commun 178:656–663

    Article  PubMed  CAS  Google Scholar 

  25. Kabututu Z, Manin M, Pointud JC, Maruyama T, Nagata N, Lambert S, Lefrancois-Martinez AM, Martinez A, Urade Y (2009) Prostaglandin f2α synthase activities of aldo–keto reductase 1b1, 1b3 and 1b7. J Biochem 145:161–168

    Article  PubMed  CAS  Google Scholar 

  26. Sugimoto Y, Hasumoto K, Namba T, Irie A, Katsuyama M, Negishi M, Kakizuka A, Narumiya S, Ichikawa A (1994) Cloning and expression of a cdna for mouse prostaglandin f receptor. J Biol Chem 269:1356–1360

    PubMed  CAS  Google Scholar 

  27. Srivastava SK, Ramana KV, Bhatnagar A (2005) Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options. Endocr Rev 26:380–392

    Article  PubMed  CAS  Google Scholar 

  28. Nishinaka T, Yabe-Nishimura C (2005) Transcription factor Nrf2 regulates promoter activity of mouse aldose reductase (AKR1B3) gene. J Pharmacol Sci 97:43–51

    Article  PubMed  CAS  Google Scholar 

  29. Jiang T, Qu JJ, Nishinaka T, Zhang N (2008) Transcription factor AP-1 regulates TGF-beta(1)-induced expression of aldose reductase in cultured human mesangial cells. Nephrology (Carlton) 13:212–217

    Article  CAS  Google Scholar 

  30. Frantz S, Fraccarollo D, Wagner H, Behr TM, Jung P, Angermann CE, Ertl G, Bauersachs J (2003) Sustained activation of nuclear factor kappa b and activator protein 1 in chronic heart failure. Cardiovasc Res 57:749–756

    Article  PubMed  CAS  Google Scholar 

  31. Hess J, Angel P, Schorpp-Kistner M (2004) Ap-1 subunits: quarrel and harmony among siblings. J Cell Sci 117:5965–5973

    Article  PubMed  CAS  Google Scholar 

  32. Lubos E, Loscalzo J, Handy DE (2010) Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. doi:10.1089/ars.2010.3586

  33. Lombardi R, Rodriguez G, Chen SN, Ripplinger CM, Li W, Chen J, Willerson JT, Betocchi S, Wickline SA, Efimov IR, Marian AJ (2009) Resolution of established cardiac hypertrophy and fibrosis and prevention of systolic dysfunction in a transgenic rabbit model of human cardiomyopathy through thiol-sensitive mechanisms. Circulation 119:1398–1407

    Article  PubMed  CAS  Google Scholar 

  34. Konno T, Chang S, Seidman JG, Seidman CE (2010) Genetics of hypertrophic cardiomyopathy. Curr Opin Cardiol. doi:10.1097/HCO.0b013e3283375698

  35. Bresson E, Boucher-Kovalik S, Chapdelaine P, Madore E, Harvey N, Laberge PY, Leboeuf M, Fortier MA (2011) The human aldose reductase akr1b1 qualifies as the primary prostaglandin f synthase in the endometrium. J Clin Endocrinol Metab 96:210–219

    Article  PubMed  CAS  Google Scholar 

  36. Lambert-Langlais S, Pointud JC, Lefrancois-Martinez AM, Volat F, Manin M, Coudore F, Val P, Sahut-Barnola I, Ragazzon B, Louiset E, Delarue C, Lefebvre H, Urade Y, Martinez A (2009) Aldo keto reductase 1b7 and prostaglandin f2α are regulators of adrenal endocrine functions. PLoS One 4:e7309

    Article  PubMed  Google Scholar 

  37. Hara S, Arai M, Tomaru K, Doi H, Koitabashi N, Iso T, Watanabe A, Tanaka T, Maeno T, Suga T, Yokoyama T, Kurabayashi M (2008) Prostaglandin f2α inhibits SERCA2 gene transcription through an induction of Egr-1 in cultured neonatal rat cardiac myocytes. Int Heart J 49:329–342

    Article  PubMed  CAS  Google Scholar 

  38. Ludman A, Venugopal V, Yellon DM, Hausenloy DJ (2009) Statins and cardioprotection—more than just lipid lowering? Pharmacol Ther 122:30–43

    Article  PubMed  CAS  Google Scholar 

  39. Senthil V, Chen SN, Tsybouleva N, Halder T, Nagueh SF, Willerson JT, Roberts R, Marian AJ (2005) Prevention of cardiac hypertrophy by atorvastatin in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circ Res 97:285–292

    Article  PubMed  CAS  Google Scholar 

  40. Alexiou P, Pegklidou K, Chatzopoulou M, Nicolaou I, Demopoulos VJ (2009) Aldose reductase enzyme and its implication to major health problems of the 21(st) century. Curr Med Chem 16:734–752

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by Research Grant of National Cerebral and Cardiovascular Center. We thank Dr. Makoto Nagano for continuous encouragement and critical reading of the manuscript, and Dr. Toshihisa Hatae for fruitful discussion.

Author information

Authors and Affiliations

  1. Laboratory of Vascular Biology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan

    Aiji Sakamoto & Yuka Sugamoto

Authors
  1. Aiji Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuka Sugamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aiji Sakamoto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakamoto, A., Sugamoto, Y. Identification of a novel aldose reductase-like gene upregulated in the failing heart of cardiomyopathic hamster. Mol Cell Biochem 353, 275–281 (2011). https://doi.org/10.1007/s11010-011-0796-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-0796-3

Keywords

Search

Navigation