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Role of RyR2 and SERCA2a in the Cardioprotective Effects of Vincanine and Pyrazoline Alkaloids

Inoyat Z. ZhumaevInstitute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanSadriddin N. BoboevInstitute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanPulat B. UsmanovInstitute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanShavkat Yu. RustamovInstitute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanAbdisalim A. ZaripovInstitute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanShakhnoza B. QurbonovaInstitute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanYulduzkhon Takhirjanovna MirzaevaInstitute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanEldor B. IbragimovInstitute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanAdilbay T. EsimbetovInstitute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, UzbekistanSh. M. AdizovInstitute of Chemistry of Plant Substances, Academy Sciences of Uzbekistan, Tashkent, Uzbekistan
Trends in Sciencesjournal2024en
ABI

Abstract

In the conducted studies, the effect of vincanine and pyrazoline indole alkaloids on cardiac muscle cell sarcoplasmic reticulum (SR) Ca2+-transport systems (RyR2 and SERCA2a) was investigated under normal and hypoxic conditions. The effect of vincanine and pyrazoline on ryanodine receptor (RyR2) was evaluated in the presence of ruthenium red and it was found that the role of RyR2 in the positive inotropic effect of these alkaloids is small. Also, in the presence of cyclopiazonic acid (IC50 = 5.6 µM), an inhibitor of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), the positive inotropic effect of vincanine and pyrazoline alkaloids was reduced. In general, the positive inotropic effects and cardioprotective properties of vincanine and pyrazoline alkaloids are mediated by modulation of SERCA2a function. HIGHLIGHTS Vincanine and pyrazoline indole alkaloids have a positive inotropic effect on the force of papillary muscle contraction of the rat heart. Vincanine and pyrazoline indole alkaloids have a cardioprotective effect and effectively eliminate the disturbances in the papillary muscle contractile activity of the rat heart caused by hypoxia. Vincanine and pyrazoline alkaloids effectively reverse hypoxia-induced SERCA2a dysfunction and normalize changes in rat cardiac papillary muscle contractile activity. GRAPHICAL ABSTRACT

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