HYDROGEN SULFIDE INCREASES CALCIUM ACCUMULATION IN CARDIAC MITOCHONDRIA AND PREVENTS CYCLOSPORINE A-SENSITIVE MITOCHONDRIAL PORE IN RAT HEART
A.Yu. Luchkova, N.A. Strutynska, V.F. Sagach
O.O. Bogomoletz Institute of Physiology National Academy
of Science of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz63.03.009
Abstract
We were studied H2S-dependent calcium accumulation in cardiac
mitochondria in condition when cyclosporine A-sensitive
mitochondrial permeability transition pore (MPTP) was not
inhibited. An active Ca2+ accumulation in organelles occurs if
it was used calcium in concentration of 5.10-5 and 10-4 mol/l,
as evidenced by the increase of Fluo-4 AM fluorescence by
46 %. It is established that hydrogen sulfide donor NaHS
showed inhibitory effect at high concentrations (10-4 mol/l)
and activating effect at low (10-7 mol/l) concentrations on the
calcium accumulation process. It was shown that mitochondrial
origin H2S also influences the mitochondrial ability to
accumulate calcium and probably increases their calcium
capacity. Thus, inhibition of H2S synthesis enzyme 3-merkaptopiruvatsulfurtransferase
by it inhibitor O-carboxymethylhidroxylamine
(O-CMH, 10-3 mol/l) significantly reduced the
rate of fluorescence. However, H2S, which is synthesized in
organelles, inhibited the formation of calcium induced MP.
Thus, the increase of H2S-dependent Ca2+ accumulation does
not causes induction of MPTP and likely leads to increase of
mitochondrial calcium capacity and, consequently, to the reduction
of this cation in the cytoplasm, which can be regarded
as one of the mechanisms for cardioprotection.
Keywords:
hydrogen sulfide; accumulation of calcium; mitochondrial pore; heart; rats
References
- Shen Y, Shen Z, Shanshan Luo, Wei Guo, and Yi Zhun Zhu. The Cardioprotective Effects of Hydrogen Sulfide in Heart Diseases: From Molecular Mechanisms to Therapeutic Potential. Ox Med and Cell Long. 2012:1–14.
- Strutynska NA, Semenykhina OM, Chorna SV, Vavilova GL, Sagach VF. Hydrogen sulfide inhibits Ca2+-induced mitochondrial permeability transition pore opening in adult and old rat heart. Fiziol Zh. 2011; 57(6):3–14. [Ukrainian].
- Munaron L, Avanzato D, Moccia F, Mancardi D. Hydrogen sulfide as a regulator of calcium channels. Cell Calcium. 2013; 53:77–84.
CrossRef
PubMed
- Glancy B, Balaban RS. Role of Mitochondrial Ca2+ in the Regulation of Cellular Energetics. Biochemistry. 2012; 51:2959–73.
CrossRef
PubMed PubMedCentral
- Bernardi P, Di Lisa F. The mitochondrial permeability transition pore: Molecular nature and role as a target in cardioprotection. J Mol. and Cell Card. 2015; 78: 100–6.
CrossRef
PubMed PubMedCentral
- Elrod JW, Calvert JW, Morrison J, Doeller JE, Kraus DW, Tao L, Jiao X, Scalia R, Kiss L, Szabo C, Kimura H, Chow CW, Lefer DJ. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci USA. 2007; 104(39):15560–5.
CrossRef
PubMed PubMedCentral
- Fu M, Zhang W, Wu L, Yang G, Li H, Wang R. Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production. PNAS. 2012; 109(8):2943–8.
CrossRef
PubMed PubMedCentral
- Guo W, Kan J, Cheng Z, Chen J, Shen Y, Xu J, Wu D, Zhu Y. Hydrogen Sulfide as an Endogenous Modulator in Mitochondria and Mitochondria Dysfunction. Ox Med and Cell Long. 2012; 1–9.
- Sagach VF, Vavilova GL, Strutyns'ka NA, Rudyk OV. The aging increase in the sensitivity of the mitochondrial permeability transition pore opening to inductors in rat heart. Fiziol Zh. 2004; 50(2): 49–63. [Ukrainian].
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; (1):265–75.
PubMed
- Budko AYu, Strutynska NA, Okhay IYu, Semenykhina OM, Sagach VF. Ca2+ accumulation in isolated rat heart mitochondria under maintenance of mitochondrial potential. Fiziol Zh. 2015; 61(6):17–25. [Ukrainian].
CrossRef
PubMed
- Kolomiets OV, Danylovych YuV, Danylovych GV, Kosterin SO. Ca2+ accumulation study in isolated smooth muscle mitochondria using Fluo-4 AM. Ukr Biochem J. 2013; 85(4):30–9. [Ukrainian].
CrossRef
- Akopova OV, Kotsiuruba AV, Tkachenko YuP, Sagach VF. Nitric oxide suppresses permeability transition pore opening and enhances calcium uptake in mitochondria in vivo. Fiziol Zh. 2005; 51(3):3–11. [Ukrainian].
PubMed
- Pan TT, Neo KL, Hu LF, Yong QC, Bian J-S. H2S preconditioning-induced PKC activation regulates intracellular calcium handling in rat cardiomyocytes. Am. J Physiol Cell Physiol. 2008; 294:169–77.
CrossRef
PubMed
- Chen Y, Zhao J, Du J, Xu G, Tang Ch, Geng B. Hydrogen sulfide regulates cardiac sarcoplasmic reticulum Ca2+ uptake via KATP channel and PI3K/Akt pathway. Life Sciences. 2012; 91:271–8.
CrossRef
PubMed
- Mys LA, Budko AYu, Strutynska NA, Sagach VF. Pyridoxal-5-phosphate restores hydrogen sulphide synthesis and redox state of heart and blood vessels tissue in old animals. Fiziol Zh. 2017; 63(1). [Ukrainian].
CrossRef
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