Regulatory role of ovarian sex hormones in calcium uptake activity of cardiac sarcoplasmic reticulum

American Journal of Physiology - Heart and Circulatory Physiology - Tập 291 Số 3 - Trang H1101-H1108 - 2006
Tepmanas Bupha‐Intr1, Jonggonnee Wattanapermpool
1Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand

Tóm tắt

Alterations in the intracellular Ca2+handling in cardiomyocytes may underlie the cardiac dysfunction observed in the ovarian sex hormone-deprived condition. To test the hypothesis that ovarian sex hormones had a significant role in the cardiac intracellular Ca2+mobilization, the sarcoplasmic reticulum (SR) Ca2+uptake and SR Ca2+-ATPase (SERCA) activity were determined in 10-wk ovariectomized rat hearts. With the use of left ventricular homogenate preparations, a significant suppression of maximum SR Ca2+uptake activity, but with an increase in SR Ca2+responsiveness, was demonstrated in ovariectomized hearts. In parallel measurements of SERCA activity in SR-enriched membrane preparations from ovariectomized hearts, a suppressed maximum SERCA activity with a leftward shift in the relationship between pCa (-log molar free Ca2+concentration) and SERCA activity was also detected. A significant downregulation of SERCA proteins and reduction in the SERCA mRNA level were observed in association with suppressed maximum SERCA activity. While there were no changes in total phospholamban and phosphorylated Ser16phospholamban levels, a decrease in phosphorylated Thr17phospholamban as well as an increase in the suprainhibitory, monomeric form of phospholamban stoichiometry was found. Estrogen and progesterone supplementations were equally effective in preventing changes in ovariectomized hearts. Our data showed for the first time that female sex hormones played an important role in the regulation of the cardiac SR Ca2+uptake. Under hormone-deficient conditions, there was an adaptive response of SERCA that escaped the regulatory effect of phospholamban.

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Tài liệu tham khảo

10.1161/01.RES.0000080932.98903.D8

10.1016/S0008-6363(03)00529-7

10.1007/s00424-003-1163-3

10.1152/japplphysiol.01227.2003

10.1152/ajpheart.1998.275.1.H264

10.1016/j.jacc.2004.05.049

10.1016/0076-6879(88)57066-0

10.1074/jbc.273.50.33674

10.1016/j.lfs.2004.12.013

10.1006/jmcc.2001.1394

10.1074/jbc.274.45.32099

10.1210/me.2003-0380

10.1016/S0008-6363(02)00694-6

10.1016/S0014-5793(97)01179-4

10.1016/S1050-1738(01)00145-1

10.1016/j.bbrc.2004.07.164

10.1007/BF00704159

Ingegno MD, Money SR, Thelmo W, Greene GL, Davidian M, Jaffe BM, and Pertschuk LP.Progesterone receptors in the human heart and great vessels.Lab Invest59: 353–356, 1988.

Jones LR, Besch HR Jr, Fleming JW, McConnaughey MM, and Watanabe AM.Separation of vesicles of cardiac sarcolemma from vesicles of cardiac sarcoplasmic reticulum. Comparative biochemical analysis of component activities.J Biol Chem254: 530–539, 1979.

Pagani EDand Solaro RJ.Method for measuring functional properties of sarcoplasmic reticulum and myofibrils in small samples of myocardium. In:Methods in Pharmacology, edited by Schwartz A. New York: Plenum, 1984, vol. 5, p. 44–61.

10.1016/j.jsbmb.2003.11.008

10.1161/01.RES.0000062469.83985.9B

10.1016/0002-9149(93)90171-8

10.1016/0378-5122(94)90099-X

10.1152/ajpheart.00866.2002

10.1126/science.1106943

Rishi AK, Shao ZM, Baumann RG, Li XS, Sheikh MS, Kimura S, Bashirelahi N, and Fontana JA.Estradiol regulation of the human retinoic acid receptor alpha gene in human breast carcinoma cells is mediated via an imperfect half-palindromic estrogen response element and Sp1 motifs.Cancer Res55: 4999–5006, 1995.

10.1161/01.RES.61.1.12

10.1074/jbc.M407879200

Toyofuku T, Curotto Kurzydlowski K, Narayanan N, and MacLennan DH.Identification of Ser38 as the site in cardiac sarcoplasmic reticulum Ca2+-ATPase that is phosphorylated by Ca2+/calmodulin-dependent protein kinase.J Biol Chem269: 26492–26496, 1994.

10.1089/104454903770238102

10.1074/jbc.M409336200

10.1093/nar/26.12.3044

10.1016/S0024-3205(98)00353-1

10.1152/ajpheart.1999.277.2.H467

10.1016/S0024-3205(99)00623-2

Wegener AD, Simmerman HK, Lindemann JP, and Jones LR.Phospholamban phosphorylation in intact ventricles. Phosphorylation of serine 16 and threonine 17 in response to beta-adrenergic stimulation.J Biol Chem264: 11468–11474, 1989.

10.1172/JCI118762

10.1161/01.RES.76.5.781

10.1006/bbrc.1999.0579

10.1100/tsw.2002.228