Role of Renin-Angiotensin System in Diabetic Heart Dysfunction and Changes in Phospholipase C Activity

  • Paramjit S. Tappia
  • Sushma A. Mengi
  • Naranjan S. Dhalla
Part of the Progress in Experimental Cardiology book series (PREC, volume 8)


The incidence of heart disease is greater in the diabetic population as compared to nondiabetics. Although cardiac abnormalities in diabetics are independent of coronary artery disease, hypertension and valvular disease, the molecular events underlying the con-tractile dysfunction of the heart during diabetes are incompletely defined. Since renin-angiotensin system is activated in diabetes, an accelerated generation of angiotensin II may be involved in the pathophysiological chain of events leading to diabetic cardiomyopathy. This article deals with the potential role of changes in phospholipase C-mediated signaling mech-anisms induced by activation of the renin-angiotensin system in diabetes. Such information will extend our knowledge in the field of heart disease due to diabetes and help in the devel-opment of new therapy for its treatment.

Key words

Diabetic cardiomyopathy Cardiac sarcolemma Phospholipase C Renin-angiotensin system Signal transduction mechanisms 


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  1. 1.
    Gargiulo P, Jacobellis G, Vaccari V, Andreani D. 1998. Diabetic cardiomyopathy: pathophysiological and clinical aspects. Diab Nutr Metab 11:336–346.Google Scholar
  2. 2.
    Mahgoub MA, Abd-Elfattah AS. 1998. Diabetes mellitus and cardiac function. Mol Cell Biochem 180:59–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Schaffer SW, Mozaffari M. 1996. Abnormal mechanical function in diabetes: relation to myocardial calcium handling. Coronary Artery Disease 7:109–115.PubMedCrossRefGoogle Scholar
  4. 4.
    Pierce GN, Beamish RE, Dhalla NS. 1988. Heart dysfunction in diabetes. 1–245. Boca Raton: CRC Press.Google Scholar
  5. 5.
    Dhalla NS, Liu X, Panagia V, Takeda N. 1998. Subcellular remodeling and heart dysfunction in chronic diabetes. Cardiovasc Res 40:239–247.PubMedCrossRefGoogle Scholar
  6. 6.
    Tomlison KC, Gardiner SM, Herdes RA, Bennet T. 1992. Functional consequences of streptozo-tocin-induced diabetes mellitus, with particular reference to the cardiovascular system. Pharmacol Rev 44:103–150.Google Scholar
  7. 7.
    Fein FS, Sonnenblick EH. Diabetic cardiomyopathy. 1994. Cardiovasc Drug Ther 8:65–73.CrossRefGoogle Scholar
  8. 8.
    Fein FS, Sonnenblick EH. 1985. Diabetic cardiomyopathy. Progr Cardiovasc Dis 27:255–270.CrossRefGoogle Scholar
  9. 9.
    Crepaldi G, Nosadini R. 1988. Diabetic cardiomyopathy: Is it a real entity. Diabetes Metab Rev 4: 273–288.PubMedCrossRefGoogle Scholar
  10. 10.
    Ren J, Davidoff AJ. 1997. Diabetes rapidly induces cardiac dysfunction in isolated ventricular myocytes. Am J Physiol 272:H148–H158.PubMedGoogle Scholar
  11. 11.
    Yu Z, Tibbits GF, McNeill JH. 1994. Cellular functions of diabetic cardiomyocytes: contractility, rapid-cooling contracture and ryanodine binding. Am J Physiol 266:H2082–H2089.PubMedGoogle Scholar
  12. 12.
    Yu JZ, Quamme GA, McNeill JH. 1995. Altered [Ca ]i mobilization in diabetic cardiomyocytes: responses to caffeine, KC1, ouabain, and ATP. Diabetes Res Clin Pract 30:9–20.PubMedCrossRefGoogle Scholar
  13. 13.
    Tamada A, Hattori Y, Houzen H, Yamada Y, Sakuma I, Kitabatake A, Kanno M. 1998. Effect of p-adrenoceptor stimulation on contractility, [Ca2+]i and Ca2+ current in diabetic rat cardiomyocytes. Am J Physiol 274:H1849–H1857.PubMedGoogle Scholar
  14. 14.
    Ha T, Kotsanas G, Wendt 1. 1999. Intracellular Ca and adrenergic responsiveness of cardiac myocytes in streptozotocin-induced diabetes. Clin Exp Pharmacol Physiol 26:347–353.PubMedCrossRefGoogle Scholar
  15. 15.
    Kotsanas G, Delbridge LM,Wendt IR. 2000. Stimulus interval-dependent differences in Ca tran-sients and contractile responses of diabetic rat cardiomyocytes. Cardiovasc Res 46:450–462.PubMedCrossRefGoogle Scholar
  16. 16.
    Hattori Y, Matsuda N, Kimura J, Ishitani T, Tamada A, Gando S, Kemmotsu O, Kanno M. 2000. Diminished function and expression of the cardiac Na+-Ca2+ exchange in diabetic rats: implications in Ca2+ overload. J Physiol 527:85–94.PubMedCrossRefGoogle Scholar
  17. 17.
    Schaffer SW. 1991. Defective calcium homeostasis in noninsulin-dependent diabetic cardiomyopa-thy. In: The Diabetic Heart. Ed. M Nagano and NS Dhalla, 183–197. New York: Raven Press.Google Scholar
  18. 18.
    Black SC McNeil JH. 1991. Functional status of the cardiac sympathetic system in diabetes. In: Catecholamines and Heart Disease. Ed. PK Ganguly, 145–161. Boca Raton: CRC Press.Google Scholar
  19. 19.
    Schafrir E. 1997. Diabetes in animals: contribution to the understanding of diabetes by study of its etiopathology in animal models. In: Ellenberg & Rifkins Diabetes Mellitus. Ed. D Porte Jr. and RS Sherwin, 301–348. Stamford: Appleton and Lange.Google Scholar
  20. 20.
    Williams SA, Tappia PS, Yu C-H, Bibeau M, Panagia V. 1998. Impaiment of the sarcolemmal phos-pholipase D-phosphatidate phosphohydrolase pathway in diabetic cardiomyopathy. J Mol Cell Cardiol 30:109–118.PubMedCrossRefGoogle Scholar
  21. 21.
    Pittman CS, Suda AK, Chambers JB Jr., McDaniel HG, Ray GY, Preston BK. 1989. Abnormalities of thyroid hormone turnover in patients with diabetes mellitus before and after insulin therapy. J Clin Endocrinol Metab 48:854–860.CrossRefGoogle Scholar
  22. 22.
    Gray RS, Borsey DO, Seth J, Herd R, Brown NS, Clarke BE 1980. Prevalence of subclinical thyroid failure in insulin-dependent diabetes. J Clin Endocrinol Metab 50:1034–1037.PubMedCrossRefGoogle Scholar
  23. 23.
    Kahaly G, Mohr-Kahaly S, Beyer J, Meyer J. 1995. Left ventricular function analyzed by Doppler and echocardiographic methods in short-term hypothyroidism. Am J Cardiol 75:645–648.PubMedCrossRefGoogle Scholar
  24. 24.
    Gay RG, Raya TE, Lancaster LD, Lee RW, Morkin E, Goldman S. 1988. Effects of thyroid state on venous compliance and left ventricular performance in rats. Am J Physiol 254:H81–H88.PubMedGoogle Scholar
  25. 25.
    Dhalla NS, Pierce GN, Innes IR, Beamish RE. 1985. Pathogenesis of cardiac dysfunction in dia-betes mellitus. Can I Cardiol 1:263–281.Google Scholar
  26. 26.
    Fiordaliso F, Li B, Latini R, Sonnenblick EH, Anversa P, Leri A, Kajstura J. 2000. Myocyte death in streptozotocin-induced diabetes in rats is angiotensin II-dependent. Lab Invest 80:513–527.PubMedCrossRefGoogle Scholar
  27. 27.
    Flack JM, Hamaty M, Staffileno BA. 1998. Renin-angiotensin-aldosterone-kinin system influences on diabetic vascular disease and cardiomyopathy. Miner Electrolyte Metab 24:412–422.PubMedCrossRefGoogle Scholar
  28. 28.
    Feuvray D, Idell-Wenger JA, Neely JR. 1979. Effects of ischemia on rat myocardial function and metabolism in diabetes. Circ Res 44:322–329.PubMedCrossRefGoogle Scholar
  29. 29.
    Duckworth WC. 2002. Hyperglycemia and cardiovascular disease. Curr Atheroscler Rep 3:383–391.CrossRefGoogle Scholar
  30. 30.
    Kikkawa R. 2000. Chronic complications in diabetes mellitus. Br J Nutr 84:Suppl. 2:S183–S185.CrossRefGoogle Scholar
  31. 31.
    Singh JP, Larson MG, O’Donnell CJ, Wilson PF, Tsuji H, Lloyd-Jones DM, Levy D 2000. Association of hyperglycemia with reduced heart rate variability (The Framingham Heart Study). Am J Cardiol 86:309–312.PubMedCrossRefGoogle Scholar
  32. 32.
    Freeman BA, Crapo JD 1982. Biology of disease. Free radicals and tissue injury. Lab Invest 47: 412–426.PubMedGoogle Scholar
  33. 33.
    Kakkar R, Kalra J, Mantha V, Prasad K. 1995. Lipid peroxidation and activity of antioxidant enzymes in diabetic rats. Mol Cell Biochem 151:113–119.PubMedCrossRefGoogle Scholar
  34. 34.
    Kakkar R, Mantha V, Kalra J, Prasad K. 1996. Time course study of oxidative stress in aorta and heart of diabetic rat. Clin Sci 91:441–448.PubMedGoogle Scholar
  35. 35.
    Mak DHF, Ip SP, Li PC, Poon MKT, Ko MN. 1996. Alterations in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats. Mol Cell Biochem 162:153–158.PubMedCrossRefGoogle Scholar
  36. 36.
    Sun F, Iwaguchi K, Shudo R, Nagaki Y, Tanaka K, Ikeda K, Tokumaru S, Kojo S. 1999. Change in tissue concentrations of lipid hydroperoxides, vitamin C and vitamin E in rats with streptozotocin-induced diabetes. Clin Sci 96:185–190.PubMedCrossRefGoogle Scholar
  37. 37.
    Giugliano D, Cariello A, Paolisso G. 1995. Diabetes mellitus, hypertension and cardiovascular disease: Which role for oxidative stress? Metabolism 44:363–368.PubMedCrossRefGoogle Scholar
  38. 38.
    Gillery P, Monboisse JC, Maquart FX, Borel JP. 1988. Glycation of proteins as a source of super-oxide. Diabetes Metab 14:25–30.Google Scholar
  39. 39.
    Wolff SP, Dean RT 1987. Glucose auto-oxidation and protein modification. The potential role of “autooxidative glycosylation” in diabetes. Biochem J 245:243–250.PubMedGoogle Scholar
  40. 40.
    Rosen P, Ballhausen T, Bloch W, Addicks K. 1995. Endothelial relaxation is disturbed by oxidative stress in the diabetic rat heart: influence of tocopherol as antioxidant. Diabetologia 38:1157–1168.PubMedCrossRefGoogle Scholar
  41. 41.
    Ceriello A, Mercuri F, Quagliaro L, Assaloni R, Motz E, Tonutti L, Taboga C. 2001. Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress. Diabetologia 44:834–838.PubMedCrossRefGoogle Scholar
  42. 42.
    Suarez-Pinzon WL, Mabley JG, Strynadka K, Power RF, Szabo C, Rabinovitch A. 2001. An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice. J Autoimmun 16:449–455.PubMedCrossRefGoogle Scholar
  43. 43.
    Yadav P, Sarkar S, Bhatnagar D. 1997. Action of capparis deciduas against alloxan-induced oxida-tive stress and diabetes in rat tissues. Pharmacol Res 36:221–228.Google Scholar
  44. 44.
    Sivian E, Recce EA, Wu YK, Homko CJ, Polansky M, Borenstein M. 1996. Dietary vitamin E pro-phylaxis and diabetic embryopathy: Morphological and biochemical analysis. Am J Obstet Gynecol 175:793–799.CrossRefGoogle Scholar
  45. 45.
    Douillet C, Chancerelle Y, Cruz C, Maroncles C, Kergonou JF, Renaud S, Ciavatti M. 1993. High dosage vitamin E effect on oxidative stress and serum lipids distribution in streptozotocin-induced diabetic rats. Biochem Med Metab Biol 50:265–276.PubMedCrossRefGoogle Scholar
  46. 46.
    Paolisso G, D’Armore A, Giugliano D, Ceriello A, Varricchio M, D’Onofrio F. 1993. Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. Am J Clin Nutr 57:650–656.PubMedGoogle Scholar
  47. 47.
    Ting HH, Timimi FK, Boles KS, Creager SJ, Ganz P, Creager MA. 1996. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 97:22–28.PubMedCrossRefGoogle Scholar
  48. 48.
    Bierhaus A, Chevion S, Chevion M, Hofman M, Quehenberger P, Illmer T, Luther T, Berentshtein E, Tritschler H, Muller M, Wahl P, Ziegler R, Nawroth PP. 1997. Advanced glycation end-product induced activation of NF KB is suppressed by alpha-lipoic acid in cultured endothelial cells. Dia-betes 46:1481–1490.CrossRefGoogle Scholar
  49. 49.
    Sechi A, Griffin CA, Shambelan M. 1994. The cardiac renin-angiotensin system in STZ-induced diabetes. Diabetes 43:1180–1184.PubMedCrossRefGoogle Scholar
  50. 50.
    Khatter JC, Sadi P, Zhang M, Hoeschen RJ. 1996. Myocardial angiotensin II (Ang II) receptors in diabetic rats. Ann NY Acad Sci 793:466–472.PubMedCrossRefGoogle Scholar
  51. 51.
    Brown L, Sernia C. 1994. Angiotensin receptors in cardiovascular diseases. Clin Exp Pharmacol Physiol 21:811–818.PubMedCrossRefGoogle Scholar
  52. 52.
    Wolf A. Free radical production, angiotensin. 2000. Curr Hypertens Rep 2:167–173.PubMedCrossRefGoogle Scholar
  53. 53.
    Rey FE, Cifuentes ME, Kiarash A, Quinn MT, Pagano PJ. 2001. Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular 02~and systolic blood pressure in mice. Circ Res 89:408–414.PubMedCrossRefGoogle Scholar
  54. 54.
    Frustaci A, Kajstura J, Chimenti QJakoniuk I, Leri A, MAseri A, Nadal-Ginard B, Anversa P. 2000. Myocardial cell death in human diabetes. Circ Res 87:1123–1132.PubMedCrossRefGoogle Scholar
  55. 55.
    Kajstura J, Fiordaliso F, Andreoli AM, Li B, Chimenti S, Medow MS, Limana F, Nadal-Ginard, Leri A, Anversa P. 2001. IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes 50:1414–1424.PubMedCrossRefGoogle Scholar
  56. 56.
    de-Cavanagh EM, Fraga CG, Ferder L, Inserra F. 1997. Enalapril and captopril enhance antioxidant defenses in mouse tissues. Am J Physiol 272:R514–R518.PubMedGoogle Scholar
  57. 57.
    de-Cavanagh EM, Inserra F, Toblli J, Stella I, Fraga CG, Ferder L. 2001. Enalapril attenuates oxida-tive stress in diabetic rats. Hypertension 38:1130–1136.PubMedCrossRefGoogle Scholar
  58. 58.
    Sand C, Peters SLM, Pfaffendorf M, van Zwieten PA. 2001. Oxidative stress impairs the haemo-dynamic activity of cardiovascular agents with antioxidant properties. Naunyn-Schmiedeberg’s Arch Pharmacol 364:454–461.CrossRefGoogle Scholar
  59. 59.
    Langer GA. 1997. Excitation-contraction coupling and calcium compartmentation. In: The Myocardium. 2nd Edition. Ed. GA Langer, 181–233. San Diego: Academic Press.CrossRefGoogle Scholar
  60. 60.
    Pierce GN, Russell JC. 1997. Regulation of intracellular Ca in the heart during diabetes. Car-diovasc Res 34:41–47.CrossRefGoogle Scholar
  61. 61.
    Heyliger CE, Prakash A, McNeill JH. 1987. Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus. Am J Physiol 253:H540–H544.Google Scholar
  62. 62.
    Makino N, Dhalla KS, Elimban V, Dhalla NS. 1987. Sarcolemmal Ca transport in streptozotocin-induced diabetic cardiomyopathy in rats. Am J Physiol 253:E202–E207.PubMedGoogle Scholar
  63. 63.
    Xu Y-J, Botsford MW, Panagia V, Dhalla NS. 1996. Responses of heart function and intracellular free Ca2+ to phosphatidic acid in chronic diabetes. Can J Cardiol 12:1092–1098.PubMedGoogle Scholar
  64. 64.
    Regan TJ, Wu CF, Yeh CK, Oldewurtel HA, Haider B. 1981. Myocardial composition and func-tion in diabetes. The effects of chronic insulin use. Circ Res 49:1268.PubMedCrossRefGoogle Scholar
  65. 65.
    Afzal N, Ganguly PK, Dhalla KS, Pierce GN, Singal PK, Dhalla NS. 1988. Beneficial effects of ver-apamil in diabetic cardiomyopathy. Diabetes 37:936–942.PubMedCrossRefGoogle Scholar
  66. 66.
    Hayashi H, Noda N. 1997. Cytosolic Ca concentration decreases in diabetic rat myocytes. Car-diovasc Res 34:99–103.CrossRefGoogle Scholar
  67. 67.
    Yu JZ, Rodrigues B, McNeill JH. 1997. Intracellular calcium levels are unchanged in the diabetic heart. Cardiovasc Res 34:91–98.PubMedCrossRefGoogle Scholar
  68. 68.
    Ziegelhoffer A, Ravingerova T, Styk J, Dzurba A, Volkovova K, Carsky J, Waczulikova I. 1998. Hearts with diabetic cardiomyopathy: adaptation to calcium overload. Wxp Clin Cardiol 3:158–160.Google Scholar
  69. 69.
    Ziegelhoffer A, Ravingerova T, Styk J, Sebokova J, Waczulikova I, Breier A, Dzurba A, Volkovova K, Carsky J, Turecky L. 1997. Mechanisms that may be involved in calcium tolerance of the diabetic heart. Mol Cell Biochem 176:191–198.PubMedCrossRefGoogle Scholar
  70. 70.
    Dhalla NS, Pierce GN, Panagia V, Singal PK, Beamish RE. 1982. Calcium movements in relation to heart function. Basic Res Cardiol 77:117–139.PubMedCrossRefGoogle Scholar
  71. 71.
    Pierce GN, Kutryk MJ, Dhalla NS. 1983. Alterations in Ca2+ binding by and composition of the cardiac sarcolemmal membrane in chronic diabetes. Proc Natl Acad Sci USA 80:5412–5416.PubMedCrossRefGoogle Scholar
  72. 72.
    Yu Z, McNeill JH. 1991. Altered inotropic responses in diabetic cardiomyopathy and hypertensive-diabetic cardiomyopathy. J Pharmacol Exp Ther 257:64–71.PubMedGoogle Scholar
  73. 73.
    Nishio Y, Kashiwagi A, Ogawa T, Asahina T, Ikebuchi M, Kodama M, Shigeta Y. 1990. Increase in [3H] PN 200–110 binding to cardiac muscle membrane in streptozotocin-induced diabetic rats. Diabetes 39:1064–1069.PubMedCrossRefGoogle Scholar
  74. 74.
    Pierce GN, Dhalla NS. 1983. Sarcolemmal Na+-K+-ATPase activity in diabetic rat heart. Am J Physiol 245:C241–C247.PubMedGoogle Scholar
  75. 75.
    Kuwahara Y, Yanagishita T, Konno N, Katagiri T. 1997. Changes in microsomal membrane phos-pholipids and fatty acids and in activities of membrane-bound enzyme in diabetic rat heart. Basic Res Cardiol 92:214–222.PubMedCrossRefGoogle Scholar
  76. 76.
    Pierce GN, Ramjiawan B, Dhalla NS, Ferrari R. 1990. Na+-H+ exchange in cardiac sarcolemmal vesicles isolated from diabetic rats. Am J Physiol 258:H255–H261.PubMedGoogle Scholar
  77. 77.
    Dhalla NS, Elimban V, Rupp H. 1992. Paradoxical role of lipid metabolism in heart function and dysfunction. Mol Cell Biochem 116:3–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Vecchini A, Del Rosso F, Binaglia L, Dhalla NS, Panagia V. 2000. Molecular defects in sarcolemmal glycerophospholipids subclasses in diabetic cardiomyopathy. J Mol Cell Cardiol 32:1061–1074.PubMedCrossRefGoogle Scholar
  79. 79.
    Okumura K, Akiyama N, Hashimoto H, Ogawa K, Satake T. 1988. Alteration of 1,2-diacylglycerol content in myocardium from diabetic rats. Diabetes 37:1168–1172.PubMedCrossRefGoogle Scholar
  80. 80.
    Okumura K, Nishiura T, Shimizu K, Iwama Y, Kondo J, Hashimoto H, Ito T. 1991. Jpn Heart J 32: 667–673.PubMedCrossRefGoogle Scholar
  81. 81.
    McHowat J, Creer MH, Hicks KK, Jones JH, McCrory R, Kennedy RH. 2000. Induction of Ca-independent PLA2 and conservation of plasmalogen polyunsaturated fatty acids in diabetic heart. Am J Physiol 279:E25–E32.Google Scholar
  82. 82.
    Ganguly PK, Beamish RE, Dhalla KS, Innes IR, Dhalla NS. 1987. Norepinephrine storage, distribution, and release in diabetic cardiomyopathy. Am J Physiol 252:E734–E739.PubMedGoogle Scholar
  83. 83.
    Wichelhaus A, Russ M, Petersen S, Eckel J. 1994. G protein expression and adenylate cyclase regulation in ventricular cardiomyocytes from STZ-diabetic rats. Am J Physiol 267:H548–H555.PubMedGoogle Scholar
  84. 84.
    De Jonge HW, van Heugten HA, LAmers JMJ. 1995. Signal transduction by the phosphatidylinos-itol cycle in myocardium. J Mol Cell Cardiol 27:93–106.PubMedCrossRefGoogle Scholar
  85. 85.
    Xiang H, McNeill JH. 1991. at-adrenoceptor-mediated phosphoinositide breakdown and inotropic responses in diabetic hearts. Am J Physiol 260:H557–H562.PubMedGoogle Scholar
  86. 86.
    Wald M, Borda ES, Sterin-Borda L. 1988. a-adrenergic supersensitivity and decreased number of OC-adrenoceptors in heart from acute diabetic rats. Can J Physiol Pharmacol 66:1154–1160.PubMedCrossRefGoogle Scholar
  87. 87.
    Rhee SG. 2001. Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem 70: 281–312.PubMedCrossRefGoogle Scholar
  88. 88.
    Tappia PS, Liu S-Y, Shatadal S, Takeda N, Dhalla NS, Panagia V. 1999. Changes in sarcolemmal PLC isoenzymes in postinfarct congestive heart failure: partial correction by imidapril. Am J Physiol 272:H40–H49.Google Scholar
  89. 89.
    Ji QS, Winnier GE, Niswender KD, Hortsman D, Wisdom R, Magnuson MA, Carpenter G. 1997. Essential role of the tyrosine kinase substrate phospholipase C-yl in mammalian growth and devel-opment. Proc Natl Acad Sci USA 94:2999–3003.PubMedCrossRefGoogle Scholar
  90. 90.
    Singer WD, Brown HA, Sternweis PC. 1997. Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D. Annu Rev Biochem 66:475–509.PubMedCrossRefGoogle Scholar
  91. 91.
    Yagisawa H, Sakuma K, Paterson HE, Cheung R, Allen V, Hirata H, Watanabe Y, Hirata M, Williams RL, Katan M. 1998. Replacements of single basic amino acids in the pleckstrin homology domain of phospholipase C-8] alter the ligand binding, phospholipase activity and interaction with the plasma membrane. J Biol Chem 273:417–424.PubMedCrossRefGoogle Scholar
  92. 92.
    James SR, Downes CR 1997. Structural and mechanistic features of phospholipase C: effectors of inositol phospholipid-mediated signal transduction. Cell Signal 9:329–336.PubMedCrossRefGoogle Scholar
  93. 93.
    Katan M. Biochim. Biophys. Acta 1998. Families of phosphoinositide-specific phospholipase C: structure and function 1436:5–17.PubMedCrossRefGoogle Scholar
  94. 94.
    Rhee SG, Bae YS. 1997. Regulation of phosphoinositide-specific phospholipase C isoenzymes. J Biol Chem 272:15045–15048.PubMedCrossRefGoogle Scholar
  95. 95.
    Lee CW, Lee KH, Lee SB, Park D, Rhee SG. 1994. Regulation of phospholipase C~P4 by ribonu-cleotides and the a subunit of Gq. J Biol Chem 269:25335–25338.PubMedGoogle Scholar
  96. 96.
    van Bilsen M. 1997. Signal transduction revisited: recent developments in angiotensin II signaling in the cardiovascular system. Cardiovasc Res 36:310–322.PubMedCrossRefGoogle Scholar
  97. 97.
    Tappia PS, Padua RR, Panagia V, Kardami K. 1999. Fibroblast growth factor-2 stimulates phos-pholipase C p in adult cardiomyocytes. Biochem Cell Biol 77:569–575.PubMedCrossRefGoogle Scholar
  98. 98.
    Sekiya F, Bae Y-S, Rhee SG. 1999. Regulation of phospholipase C isoenzymes: activation of phos-pholipase C-y in the absence of tyrosine-phosphorylation. Chem Phys Lipids 98:3–11.PubMedCrossRefGoogle Scholar
  99. 99.
    Im H-J, Russell MA, Feng J-F. 1997. Transglutaminase II: a new class of GTP-binding protein with new biological functions. Cell Signal 9:477–482.PubMedCrossRefGoogle Scholar
  100. 100.
    Park H, Park ES, Lee HS, Yun HY, Kwon NS, Baek KJ. 2001. Distinct characteristic of Gah (trans-glutaminase II) by compartment: GTPase and transglutaminase activities. Biochem Biophys Res Commun 284:496–500.PubMedCrossRefGoogle Scholar
  101. 101.
    Lopez I, Mak EJ, Ding J, Hamm HE, Lomasney JW. 2001. A novel bifunctional phopsholipase C that is regulated by Gal2 and stimulates the Ras/mitogen-activated protein kinase pathway. J Biol Chem 276:2758–2765.PubMedCrossRefGoogle Scholar
  102. Wolf RA. 1993. Specific expression of phospholipase C-8t and by adult cardiac ventricular myocytes (Abstract) Circulation 88 Suppl. 1:1–241.Google Scholar
  103. 103.
    Wolf RA. 1992. Association of phospholipase C-8 with a highly enriched preparation of canine sarcolemma. Am J Physiol 263:C1021–C1028.PubMedGoogle Scholar
  104. 104.
    Gonzalez-Yanes C, Santos-Alvarez J, Sanchez-Margalet V. 2001. Pancreastatin, a chromogranin A- derived peptide, activates Gat6 and phospholipase C-P2 by interacting with specific receptors in rat heart membranes. Cell Signal 13:43–49.PubMedCrossRefGoogle Scholar
  105. 105.
    Song C, Hu CD, Masago M, Kariyai K, Yamawaki-Kataoka Y, Shibatohge M, Wu D, Satoh T, Kataoka T. 2001. Regulation of a novel human phospholipase C, PLCe, through membrane targeting by Ras. J Biol Chem 276:2752–2757.PubMedCrossRefGoogle Scholar
  106. 106.
    Arthur JF, Matkovich SJ, Mitchell CJ, Biden TJ, Woodcock EA. 2001. Evidence for selective cou-pling of (Xi-adrenergic receptors to phospholipase C-pt in rat neonatal cardiomyocytes. J Biol Chem 276:37341–37346.PubMedCrossRefGoogle Scholar
  107. 107.
    Huisamen B, Mouton R, Opie LH, Lochner A. 1994. Demonstration of a specific [3H]Ins(l,4,5)P3 binding site in rat heart sarcoplasmic reticulum. J Mol Cell Cardiol 26:341–349.PubMedCrossRefGoogle Scholar
  108. 108.
    Kijima Y, Fleischer S. 1992. Two types of inositol trisphosphate binding in cardiac microsomes. Biochem Biophys Res Commun 189:728–735.PubMedCrossRefGoogle Scholar
  109. 109.
    Gilbert JC, Shirayama T, Pappano AJ. 1991. Inositol trisphosphate promotes Na-Ca exchange current by releasing calcium from sarcoplasmic reticulum in cardiac myocytes. Circ Res 69:1632–1639.PubMedCrossRefGoogle Scholar
  110. 110.
    Jaconi M, Bony C, Richards SM, Terzic A, Arnaudeau, Vassort G, Pucéat M. 2000. Inositol 1,4,5- trisphosphate directs Ca2+ flow between mitochondria and the endoplasmic/sarcoplasmic reticulum: a role in regulating cardiac autonomic Ca2+ spiking. Mol Biol Cell 11:1845–1858.PubMedGoogle Scholar
  111. 111.
    Quist EE, Foresman BH, Vasan R, Quist CW 1994. Inositol tetrakisphosphate stimulates a novel ATP-dependent Ca 2+ uptake mechanism in cardiac junctional sarcoplasmic reticulum. Biochem Biophys Res Commun 204:69–75.PubMedCrossRefGoogle Scholar
  112. 112.
    Puceat M, Vassort G. 1996. Signalling by protein kinase C isoforms in the heart. Mol Cell Biochem 157:65–72.PubMedCrossRefGoogle Scholar
  113. 113.
    Kijima Y, Saito A, Jetton JL, Magnuson MA, Fleischer S. 1993. Different intracellular localization of inositol 1,4,5-trisphosphate and ryanodine receptors in cardiomyocytes. J Biol Chem 268: 3499–3506.PubMedGoogle Scholar
  114. 114.
    Jalili T, Takeishi Y, Song G, Ball NA, Howies G, Walsh RA. 1999. PKC translocation without changes in G(Xq and PLC-p protein abundance in cardiac hypertrophy and failure. Am J Physiol 277: H2298–H22304.PubMedGoogle Scholar
  115. 115.
    Jalili T, Takeishi Y, Walsh RA. 1999. Signal transduction during cardiac hypertrophy: the role of Gotq, PLC-Pl, and PKC. Cardiovasc Res 44:5–9.PubMedCrossRefGoogle Scholar
  116. 116.
    Quest AFG, Raben DM, Bell RM. 1996. Diacylglycerols-biosynthetic intermediates and lipid second messengers. In: Handbook of Lipid Research. Lipid Second Messengers. Ed. RM Bell, JH Exton and SE Prescott, Vol 8, 1–58. New York: Plenum Press.Google Scholar
  117. 117.
    Billah MM. Phospholipase D and cell signaling. 1993. Curr Opin Immunol 5:114–123.PubMedCrossRefGoogle Scholar
  118. 118.
    Hodgkin MN, Pettitt TR, Martin A, Michell RH, Pemberton AJ, Wakelam MJ. 1998. Diacylglyc-erols and phosphatidates: which molecular species are intracellular messengers? Trends Biochem Sci 23:200–204.PubMedCrossRefGoogle Scholar
  119. 119.
    Malhotra A, Reich D, Reich D, Nakouzi A, Sanghi V, Geenen DL, Buttrick PM. 1997. Experi-mental diabetes is associated with functional activation of protein kinase Ce and phosphorylation of troponin I in the heart, which are prevented by angiotensin II receptor blockade. Circ Res 81:1027–1033.PubMedCrossRefGoogle Scholar
  120. 120.
    Malhotra A, Kang BP, Cheung S, Opawumi D, Meggs LG. 2001. Angiotensin II promotes glucose-induced activation of cardiac protein kinase C isozymes and phosphorylation of troponin I. Dia-betes 50:1918–1926.CrossRefGoogle Scholar
  121. 121.
    Xiang H, McNeill JH. 1992. Protein kinase C activity is altered in diabetic rat hearts. Biochem Biophys Res Commun 187:703–710.PubMedCrossRefGoogle Scholar
  122. 122.
    Tanaka Y, Kashiwagi T, Ogawa T, Abe T, Asahina M, Ikebuchi Y, Takagi Y, Shigeta Y 1991. Effect of verapamil on cardiac protein kinase C activity in diabetic hearts. Eur J Pharmacol 200:353–356.PubMedCrossRefGoogle Scholar
  123. 123.
    Liu X, Wang J, Takeda N, Binaglia L, Panagia V, Dhalla NS. 1999. Changes in cardiac protein kinase C activities and isozymes in streptozotocin-induced diabetes. Am J Physiol 277:E798–E804.PubMedGoogle Scholar
  124. 124.
    Liu S-Y, Yu C-H, Hays J-A, Panagia V, Dhalla NS. 1997. Modification of heart sarcolemmal phos-phoinositide pathway by lysophosphatidylcholine. Biochim Biophys Acta 1349:264–274.PubMedCrossRefGoogle Scholar
  125. 125.
    Mesaeli N, Tappia PS, Suzuki S, Dhalla NS, Panagia V. 2000. Oxidants depress the synthesis of phos-phatidylinositol 4,5-bisphosphate in heart sarcolemma. Arch Biochem Biophys 382:48–56.PubMedCrossRefGoogle Scholar
  126. 126.
    Meij JTA, Suzuki S, Panagia V, Dhalla NS. 1994. Oxidative stress modifies the activity of cardiac sarcolemmal phospholipase C. Biochim Biophys Acta 1199:6–12.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Paramjit S. Tappia
    • 1
  • Sushma A. Mengi
    • 1
  • Naranjan S. Dhalla
    • 1
  1. 1.Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Departments of Human Nutritional Sciences and Physiology, Faculties of Human Ecology and MedicineUniversity of ManitobaWinnipegCanada

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