Characterization of Glutathione Dithiophosphates as Long-Acting H2S Donors

被引:0
|
作者
Ishkaeva, Rezeda A. A. [1 ,2 ]
Khaertdinov, Nail N. N. [1 ]
Yakovlev, Aleksey V. V. [1 ]
Esmeteva, Marina V. V. [1 ,2 ]
Salakhieva, Diana V. V. [1 ,2 ]
Nizamov, Ilyas S. S. [3 ,4 ]
Sitdikova, Guzel F. F. [1 ]
Abdullin, Timur I. I. [1 ,2 ]
机构
[1] Kazan Volga Reg Fed Univ, Inst Fundamental Med & Biol, 18 Kremlyovskaya St, Kazan 420008, Russia
[2] Kazan Volga Reg Fed Univ, Sci & Educ Ctr Pharmaceut, 18 Kremlyovskaya St, Kazan 420008, Russia
[3] Kazan Volga Reg Fed Univ, Alexander Butlerov Inst Chem, Kazan 420008, Russia
[4] FRC Kazan Sci Ctr RAS, Arbuzov Inst Organ & Phys Chem, 8 Arbuzov St, Kazan 420088, Russia
基金
俄罗斯科学基金会;
关键词
hydrogen sulfide; donors; glutathione; dithiophosphates; myoblasts; myocytes; reactive oxygen species; atrial myocardium; contraction; negative inotropic effect; HYDROGEN-SULFIDE DONORS; CELL; DIFFERENTIATION; CHANNELS; RAT; CHEMISTRY; CALCIUM; BIOLOGY; INJURY; FROG;
D O I
10.3390/ijms241311063
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Considering the important cytoprotective and signaling roles but relatively narrow therapeutic index of hydrogen sulfide (H2S), advanced H2S donors are required to achieve a therapeutic effect. In this study, we proposed glutathione dithiophosphates as new combination donors of H2S and glutathione. The kinetics of H2S formation in dithiophosphate solutions suggested a continuous H2S release by the donors, which was higher for the dithiophosphate of reduced glutathione than oxidized glutathione. The compounds, unlike NaHS, inhibited the proliferation of C2C12 myoblasts at submillimolar concentrations due to an efficient increase in intracellular H2S. The H2S donors more profoundly affected reactive oxygen species and reduced glutathione levels in C2C12 myocytes, in which these parameters were elevated compared to myoblasts. Oxidized glutathione dithiophosphate as well as control donors exerted antioxidant action toward myocytes, whereas the effect of reduced glutathione dithiophosphate at (sub-)micromolar concentrations was rather modulating. This dithiophosphate showed an enhanced negative inotropic effect mediated by H2S upon contraction of the atrial myocardium, furthermore, its activity was prolonged and reluctant for washing. These findings identify glutathione dithiophosphates as redox-modulating H2S donors with long-acting profile, which are of interest for further pharmacological investigation.
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页数:15
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