EFEK PEMBERIAN KALSITRIOL (1α,25 (OH)2 D3) TERHADAP KADAR CYCLIC AMP KULTUR KARDIOMIOSIT
Abstract
Defisiensi kalsitriol dapat meningkatkan faktor risiko terjadinya penyakit kardiovaskular. Hal ini dikaitkan dengan penurunan fosforilasi troponin I (TnI) di Ser23/24. Fosforilasi TnI di Ser23/24 berperan dalam regulasi Mg-ATPase miofilamen dan sensitivitas miofilamen terhadap Ca2+ yang selanjutnya mempengaruhi respon frekuensi dan kekuatan ejeksi ventrikel. Ser23/24 TnI ini diketahui merupakan substrat spesifik PKA. Penelitian ini bertujuan untuk mempelajari apakah efek kalsitriol terhadap peningkatan fosforilasi TnI mempunyai jalur mekanisme aksi yang juga melalui cAMP/PKA. Penelitian ini merupakan eksperimental murni menggunakan rancangan pre-post test with control group dengan sampel kultur primer kardiomiosit Sprague-Dawley jantan dewasa. Kardiomiosit diinkubasi kalsitriol selama 5 menit kemudian kadar cAMP diukur menggunakan metode ELISA. Hasil penelitian tidak menunjukkan adanya korelasi antara peningkatan TnI terfosforilasi dengan kadar cAMP (p>0,05). Penelitian ini masih belum dapat membuktikan adanya jalur aktivasi cAMP/PKA oleh kalsitriol dalam mekanisme peningkatan TnI terfosforilasi pada kardiomiosit.
Keywords
Full Text:
PDFReferences
Pilz S, März W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab 2008;93:3927-3935.
Messer AE, Jacques AM, Marston SB. Troponin I phosphorylation and regulatory function in human heart muscle: dephosphorylation of Ser23/24 on troponin I could account for the contractile defect in end-stage heart failure. J Mol Cell Cardiol 2007;42(1):247-59.
Pi Y, Zhang D, Kemnitz KR, Wang H, Walker JW. Protein kinase C and A sites on troponin I regulate myofilament Ca2+ sensitivity and ATPase activity in the mouse myocardium. J Physiol 2003;552(3):845-57.
Messer AE, Marston SB. Investigating the role of uncoupling of troponin I phosphorilation from changes in myofibrillar Ca2+-sensitivity in the pathogenesis of cardiomyopathy. Front Physiol 2014;5:315.
Bodor GS, Oakeley AE, Allen PD, Crimmins DL, Ladenson JH, Anderson PAW. Troponin I phosphorilation in the normal and failing adult human heart. Circulation 1997;96(5):1495-500.
Zhao G, Simpson RU. Interaction between vitamin D receptor with caveolin-3 and regulation by 1,25-dihydroxyvitamin D3 in adult rat cardiomyocytes. J Steroid Biochem Mol Biol 2010;121(1-2):159–63.
Green JJ, Robinson DA, Wilson GE, Simpson RU, Westfall MV. Calcitriol modulation of cardiac contractile performance via protein kinase C. J Mol Cell Cardiol 2006;41(2):350–9.
Ün İ, Kurt AH, Batuş A, Büyükafşar K. Alfacalcidol suppresses α-receptor–mediated vasoconstriction via an endothelium dependent mechanism. Turk J Med Sci 2013;43:238–244.
Tishkoff DX, Nibbelink KA, Holmberg KH, Dandu L, Simpson RU. Functional vitamin D receptor (VDR) in the T-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility. Endocrinology 2008;149(2):558-564.
Rapundalo ST. Cardiac protein phosphorylation: functional and pathophysiological correlates. Cardiovasc Res 1998;38(3):559–88.
Yamashita N, Hoshida S, Nishida M, Igarashi J, Taniguchi N, Tada M et al. Heat shock-induced manganese superoxide dismutase enhances the tolerance of cardiac myocytes to hypoxia–reoxygenation injury. J Mol Cell Cardiol 1997;29:1805–1813.
Solaro RJ, Rosevear P, Kobayashi T. The unique function of cardiac troponin I in the control of cardiac muscle contraction and relaxation. Biochem Biophys Res Commun 2008;369(1): 82-87.
Hoit BD, Walsh RA. Normal physiology of the cardiovascular system. In Fuster V, Walsh RA, O'Rourke RA, Poole-Wilson P, editors. Hurst's The Heart. New York: McGraw-Hill, 2008:83-109.
Guyton AC, Hall JE. Buku Ajar Fisiologi Kedokteran. Ed. 11. Jakarta: EGC, 2008.
Noland TA, Guo X, Raynor RL, Jideama NM, Averyhart-Fullard V, Solaro J, Kuo JF. Cardiac troponin I mutants: phosphorylation by protein kinases C and A and regulation of Ca2+-stimulated MgATPase of reconstituted actomyosin S-1. J Biol Chem 1995;270:25445-54.
Swiderek K, Jaquet K, Meyer HE, Schachtele C, Hofmann F, Heilmeyer LMG. Sites phosphorylated in bovine cardiac troponin T and I: Characterization by 'P-NMR spectroscopy and phosphorylation by protein kinases. Eur J Biochem 1990;190:575-82.
DOI: https://doi.org/10.29103/averrous.v1i2.397
Article Metrics
Abstract Views : 279 times
PDF Downloaded : 60 times
Refbacks
- There are currently no refbacks.
Copyright (c) 2018 Cut Sidrah Nadira
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
| Print ISSN | : |
2477-5231 |
| Online ISSN |
: |
2502-8715 |
Publisher:
Fakultas Kedokteran Universitas Malikussaleh
Kampus Fakultas Kedokteran Universitas Malikussaleh, Jl. Meunasah, Uteunkot Cunda, Lhokseumawe, 24351, Provinsi Aceh, Tel/fax : 081376575984, Email: averrous@unimal.ac.id
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.