EFEK PEMBERIAN KALSITRIOL (1α,25 (OH)2 D3) TERHADAP KADAR CYCLIC AMP KULTUR KARDIOMIOSIT

Cut Sidrah Nadira

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


kalsitriol, kontraktilitas, kardiomiosit, troponin I

Full Text:

PDF

References


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 : 339 times
 PDF Downloaded : 63 times

Refbacks

  • There are currently no refbacks.


Copyright (c) 2018 Cut Sidrah Nadira

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.


Print ISSN :
2477-5231
Online  ISSN
:
2502-8715

Publisher:
Unimal Logo

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

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.