Horm Metab Res 2009; 41(8): 594-599
DOI: 10.1055/s-0029-1216374
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Heat Shock Protein 27 Modification is Increased in the Human Diabetic Failing Heart

T. Gawlowski 1 [*] , B. Stratmann 1 [*] , I. Stork 1 , B. Engelbrecht 1 , A. Brodehl 1 , K. Niehaus 3 , R. Körfer 2 , D. Tschoepe 1 , H. Milting 2
  • 1Heart and Diabetes Center NRW, Ruhr-University Bochum for the Meta-Card Research Group, Diabetes Center, Bad Oeynhausen, Germany
  • 2Heart and Diabetes Center NRW, Ruhr-University Bochum for the Meta-Card Research Group, Erich & Hanna Klessmann-Institute, Bad Oeynhausen, Germany
  • 3Bielefeld University, Proteom and Metabolom Research, Faculty of Biology, Bielefeld, Germany
Further Information

Publication History

received 15.12.2008

accepted 19.02.2009

Publication Date:
21 April 2009 (online)

Abstract

Chronic conditions like diabetes mellitus (DM) leading to altered metabolism might cause cardiac dysfunction. Hyperglycemia plays an important role in the pathogenesis of diabetic complications including accumulation of methylglyoxal (MG), a highly reactive α-dicarbonyl metabolite of glucose degradation pathways and increased generation of advanced glycation endproducts (AGEs). The aim of this investigation was to study the extent of the MG-modification argpyrimidine in human diabetic heart and in rat cardiomyoblasts grown under hyperglycemic conditions. Left ventricular myocardial samples from explanted hearts of patients with cardiomyopathy with (n=8) or without DM (n=8) as well as nonfailing donor organs (n=6), and rat cardiac myoblasts H9c2 treated with glucose were screened for the MG-modification argpyrimidine. The small heat shock protein 27 (Hsp27) revealed to be the major argpyrimidine containing protein in cardiac tissue. Additionally, the modification of arginine leading to argpyrimidine and the phosphorylation of Hsp27 are increased in the myocardium of patients with DM. In H9c2 cells hyperglycemia leads to a decrease of the Hsp27-expression and an increase in argpyrimidine content and phosphorylation of Hsp27, which was accompanied by the induction of oxidative stress and apoptosis. This study shows an association between diabetes and increased argpyrimidine-modification of myocardial Hsp27, a protein which is involved in apoptosis, oxidative stress, and cytoskeleton stabilization.

References

  • 1 Brownlee M. Biochemistry and molecular cell biology of diabetic complications.  Nature. 2001;  414 813-820
  • 2 Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.  N Engl J Med. 1998;  339 229-234
  • 3 Poornima IG, Parikh P, Shannon RP. Diabetic cardiomyopathy: the search for a unifying hypothesis.  Circ Res. 2006;  98 596-605
  • 4 Bucala R, Cerami A. Advanced glycosylation: chemistry, biology, and implications for diabetes and aging.  Adv Pharmacol. 1992;  23 1-34
  • 5 Bunn HF, Higgins PJ. Reaction of monosaccharides with proteins: possible evolutionary significance.  Science. 1981;  213 222-224
  • 6 Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications.  N Engl J Med. 1988;  318 1315-1321
  • 7 Cooper ME. Importance of advanced glycation end products in diabetes-associated cardiovascular and renal disease.  Am J Hypertens. 2004;  17 31S-38S
  • 8 Sell DR, Lapolla A, Odetti P, Fogarty J, Monnier VM. Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM.  Diabetes. 1992;  41 1286-1292
  • 9 Bidasee KR, Zhang Y, Shao CH, Wang M, Patel KP, Dincer UD, Besch Jr HR. Diabetes increases formation of advanced glycation end products on Sarco(endo)plasmic reticulum Ca2+-ATPase.  Diabetes. 2004;  53 463-473
  • 10 Lee AG, East JM. What the structure of a calcium pump tells us about its mechanism.  Biochem J. 2001;  356 665-683
  • 11 Sweadner KJ, Donnet C. Structural similarities of Na, K-ATPase and SERCA, the Ca(2+)-ATPase of the sarcoplasmic reticulum.  Biochem J. 2001;  356 685-704
  • 12 Berlanga J, Cibrian D, Guillen I, Freyre F, Alba JS, Lopez-Saura P, Merino N, Aldama A, Quintela AM, Triana ME, Montequin JF, Ajamieh H, Urquiza D, Ahmed N, Thornalley PJ. Methylglyoxal administration induces diabetes-like microvascular changes and perturbs the healing process of cutaneous wounds.  Clin Sci (Lond). 2005;  109 83-95
  • 13 Lapolla A, Flamini R, Vedova A, Senesi A, Reitano R, Fedele D, Basso E, Seraglia R, Traldi P. Glyoxal and Methylglyoxal Levels in Diabetic Patients: Quantitative Determination by a New GC/MS Method.  Clin Chem Lab Med. 2003;  41 1166-1173
  • 14 Shinohara M, Thornalley PJ, Giardino I, Beisswenger P, Thorpe SR, Onorato J, Brownlee M. Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis.  J Clin Invest. 1998;  101 1142-1147
  • 15 Randell EW, Vasdev S, Gill V. Measurement of methylglyoxal in rat tissues by electrospray ionization mass spectrometry and liquid chromatography.  J Pharmacol Toxicol Methods. 2005;  51 153-157
  • 16 Ahmed N, Thornalley PJ. Peptide mapping of human serum albumin modified minimally by methylglyoxal in vitro and in vivo.  Ann N Y Acad Sci. 2005;  1043 260-266
  • 17 Padival AK, Crabb JW, Nagaraj RH. Methylglyoxal modifies heat shock protein 27 in glomerular mesangial cells.  FEBS Lett. 2003;  551 113-118
  • 18 Sakamoto H, Mashima T, Yamamoto K, Tsuruo T. Modulation of heat-shock protein 27 (Hsp27) anti-apoptotic activity by methylglyoxal modification.  J Biol Chem. 2002;  277 45770-45775
  • 19 Schalkwijk CG, van Bezu J, van der Schors RC, Uchida K, Stehouwer CD, van Hinsbergh VW. Heat-shock protein 27 is a major methylglyoxal-modified protein in endothelial cells.  FEBS Lett. 2006;  580 1565-1570
  • 20 van Heijst JW, Niessen HW, Musters RJ, van Hinsbergh VW, Hoekman K, Schalkwijk CG. Argpyrimidine-modified Heat shock protein 27 in human non-small cell lung cancer: a possible mechanism for evasion of apoptosis.  Cancer Lett. 2006;  241 309-319
  • 21 Pichon S, Bryckaert M, Berrou E. Control of actin dynamics by p38 MAP kinase – Hsp27 distribution in the lamellipodium of smooth muscle cells.  J Cell Sci. 2004;  117 2569-2577
  • 22 Ibitayo AI, Sladick J, Tuteja S, Louis-Jacques O, Yamada H, Groblewski G, Welsh M, Bitar KN. HSP27 in signal transduction and association with contractile proteins in smooth muscle cells.  Am J Physiol. 1999;  277 G445-G454
  • 23 Milting H, Scholz C, Arusoglu L, Freitag M, Cebulla R, Jaquet K, Korfer R, D VL, Kassner A, Brodde OE, Kogler H, El Banayosy A, Pieske B. Selective upregulation of beta1-adrenergic receptors and dephosphorylation of troponin I in end-stage heart failure patients supported by ventricular assist devices.  J Mol Cell Cardiol. 2006;  41 441-450
  • 24 Milting H, Kassner A, Arusoglu L, Meyer HE, Morshuis M, Brendel R, Klauke B, El Banayosy A, Korfer R. Influence of ACE-inhibition and mechanical unloading on the regulation of extracellular matrix proteins in the myocardium of heart transplantation candidates bridged by ventricular assist devices.  Eur J Heart Fail. 2006;  8 278-283
  • 25 Oya T, Hattori N, Mizuno Y, Miyata S, Maeda S, Osawa T, Uchida K. Methylglyoxal modification of protein. Chemical and immunochemical characterization of methylglyoxal-arginine adducts.  J Biol Chem. 1999;  274 18492-18502
  • 26 Galderisi M, Anderson KM, Wilson PW, Levy D. Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study).  Am J Cardiol. 1991;  68 85-89
  • 27 Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.  BMJ. 2000;  321 405-412
  • 28 Ren J, Davidoff AJ. Diabetes rapidly induces contractile dysfunctions in isolated ventricular myocytes.  Am J Physiol. 1997;  272 H148-H158
  • 29 Huot J, Houle F, Spitz DR, Landry J. HSP27 phosphorylation-mediated resistance against actin fragmentation and cell death induced by oxidative stress.  Cancer Res. 1996;  56 273-279
  • 30 Kuethe F, Sigusch HH, Bornstein SR, Hilbig K, Kamvissi V, Figulla HR. Apoptosis in patients with dilated cardiomyopathy and diabetes: a feature of diabetic cardiomyopathy?.  Horm Metab Res. 2007;  39 672-676
  • 31 Oya-Ito T, Liu BF, Nagaraj RH. Effect of methylglyoxal modification and phosphorylation on the chaperone and anti-apoptotic properties of heat shock protein 27.  J Cell Biochem. 2006;  99 279-291
  • 32 Desai KM, Wu L. Free radical generation by methylglyoxal in tissues.  Drug Metabol Drug Interact. 2008;  23 151-173
  • 33 Pleissner KP, Soding P, Sander S, Oswald H, Neuss M, Regitz-Zagrosek V, Fleck E. Dilated cardiomyopathy-associated proteins and their presentation in a WWW-accessible two-dimensional gel protein database.  Electrophoresis. 1997;  18 802-808
  • 34 Chowdhry MF, Vohra HA, Galinanes M. Diabetes increases apoptosis and necrosis in both ischemic and nonischemic human myocardium: role of caspases and poly-adenosine diphosphate-ribose polymerase.  J Thorac Cardiovasc Surg. 2007;  134 124-131 , 131 e121–e123
  • 35 Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, Nadal-Ginard B, Anversa P. Myocardial cell death in human diabetes.  Circ Res. 2000;  87 1123-1132
  • 36 Shimoni Y, Rattner JB. Type 1 diabetes leads to cytoskeleton changes that are reflected in insulin action on rat cardiac K(+) currents.  Am J Physiol Endocrinol Metab. 2001;  281 E575-E585

1 These authors contributed equally to the work.

Correspondence

H. MiltingPhD 

Heart and Diabetes Center

NRW

Ruhr-University Bochum

Georgstraße 11

32545 Bad Oeynhausen

Germany

Phone: +49/5731/97 35 10

Fax: +49/5731/97 24 76

Email: hmilting@hdz-nrw.de

    >