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Preconditioning the rat heart with sodium thiosulfate preserved the mitochondria in response to ischemia-reperfusion injury

  • Sriram Ravindran
  • Gino A. KurianEmail author
Article

Abstract

Sodium thiosulfate preconditioning (SIPC) was recently reported to be cardioprotective due to its ability to inhibit caspase-3 activation, chelate calcium ions and scavenge free radicals. However, the rationale behind its ability to improve the contractility of isolated rat heart challenged with ischemia-reperfusion injury (IR) is not well understood. As mitochondrial preservation is implicated in cardioprotection against IR, the present study was conceived to identify whether the cardioprotective effects of SIPC is associated with mitochondrial preservation. Using the isolated Langendorff rat heart model, 1 mM sodium thiosulfate (STS) was used to precondition the rat heart before IR and was used to study its effect on cardiac mitochondria. The IR heart experienced a ventricular contractile dysfunction that was improved by SIPC. Upon assessing in-gel the ATP synthetic capacity of mitochondria from IR heart, there was a significant decline, while in SIPC it was well preserved close to sham. As a sustained flow of electrons through the ETC and well-integrated mitochondria are the prerequisites for ATP synthesis, SIPC improved the activities of ETC complex enzymes (I-IV), which was reflected from the preserved ultrastructure of the mitochondria as analyzed from electron-microscopy in the treated rat hearts. This observation was coherent with the elevated expression of PGC1α (20%), a critical regulator of ATP production, which increased the mitochondrial copy number as well in the STS treated heart compared to IR. In conclusion, mitochondria might be a critical target for SIPC mediated cardioprotection against IR.

Keywords

Sodium thiosulfate preconditioning Inter-fibrillar mitochondria Sub-sarcolemmal mitochondria Complex-V ATP PGC-1alpha 

Notes

Acknowledgements

We would like to acknowledge the Indian Council of Medical Research (ICMR), New Delhi, India [No.5/4/1-14/12-NCD-II], for funding this research by providing a grant to Dr. Gino A. Kurian.

Supplementary material

10863_2019_9794_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 15 kb)

References

  1. Barrientos A, Fontanesi F, Díaz F (2009) Evaluation of the Mitochondrial Respiratory Chain and Oxidative Phosphorylation System using Polarography and Spectrophotometric Enzyme Assays Current protocols in human genetics / editorial board, Jonathan L Haines [et al] CHAPTER:Unit19.13-Unit19.13.  https://doi.org/10.1002/0471142905.hg1903s63
  2. Crochemore C, Mekki M, Corbière C, Karoui A, Noël R, Vendeville C, Vaugeois JM, Monteil C (2015) Subsarcolemmal and interfibrillar mitochondria display distinct superoxide production profiles. Free Radic Res 49:331–337.  https://doi.org/10.3109/10715762.2015.1006212 CrossRefGoogle Scholar
  3. De Gubareff T, Furchgott RF (1956) The determination of inorganic phosphate and creatine phosphate in tissue extracts. J Biol Chem 223:377–388Google Scholar
  4. Halestrap AP, Pasdois P (2009) The role of the mitochondrial permeability transition pore in heart disease. Biochim Biophys Acta (BBA) - Bioenerg 1787:1402–1415.  https://doi.org/10.1016/j.bbabio.2008.12.017 CrossRefGoogle Scholar
  5. Hausenloy DJ, Yellon DM (2013) Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest 123:92–100.  https://doi.org/10.1172/JCI62874 CrossRefGoogle Scholar
  6. Holmuhamedov EL, Oberlin A, Short K, Terzic A, Jahangir A (2012) Cardiac subsarcolemmal and interfibrillar mitochondria display distinct responsiveness to protection by diazoxide. PLoS One 7:e44667.  https://doi.org/10.1371/journal.pone.0044667 CrossRefGoogle Scholar
  7. Hong-jie C et al (2017) Progress in therapies for myocardial ischemia reperfusion. Inj Curr Drug Targets 18:1712–1721.  https://doi.org/10.2174/1389450117666160401120308 Google Scholar
  8. Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura KI, Utsumi H, Hamasaki N, Takeshita A (2001) Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 88:529–535CrossRefGoogle Scholar
  9. Jennings RB, Sommers HM, Smyth GA, Flack HA, Linn H (1960) Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol 70:68–78Google Scholar
  10. Ju J, Huang C, Minskoff SA, Mayotte JE, Taillon BE, Simons JF (2003) Simultaneous gene expression analysis of steady-state and actively translated mRNA populations from osteosarcoma MG-63 cells in response to IL-1alpha via an open expression analysis platform. Nucleic Acids Res 31:5157–5166CrossRefGoogle Scholar
  11. Kaasik A, Joubert F, Ventura-Clapier R, Veksler V (2004) A novel mechanism of regulation of cardiac contractility by mitochondrial functional state. FASEB J 18:1219–1227.  https://doi.org/10.1096/fj.04-1508com CrossRefGoogle Scholar
  12. Karamanlidis G, Nascimben L, Couper GS, Shekar PS, del Monte F, Tian R (2010) Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ Res 106:1541–1548.  https://doi.org/10.1161/CIRCRESAHA.109.212753 CrossRefGoogle Scholar
  13. Kobayashi T, Kuroda S, Tada M, Houkin K, Iwasaki Y, Abe H (2003) Calcium-induced mitochondrial swelling and cytochrome c release in the brain: its biochemical characteristics and implication in ischemic neuronal injury. Brain Res 960:62–70CrossRefGoogle Scholar
  14. Kurian GA, Berenshtein E, Kakhlon O, Chevion M (2012) Energy status determines the distinct biochemical and physiological behavior of interfibrillar and sub-sarcolemmal mitochondria. Biochem Biophys Res Commun 428:376–382.  https://doi.org/10.1016/j.bbrc.2012.10.062 CrossRefGoogle Scholar
  15. Liu Y, Beyer A, Aebersold R (2016) On the dependency of cellular protein levels on mRNA abundance. Cell 165:535–550.  https://doi.org/10.1016/j.cell.2016.03.014 CrossRefGoogle Scholar
  16. Lu Z, Xu X, Hu X, Fassett J, Zhu G, Tao Y, Li J, Huang Y, Zhang P, Zhao B, Chen Y (2010) PGC-1α regulates expression of myocardial mitochondrial antioxidants and myocardial oxidative stress after chronic systolic overload. Antioxid Redox Signal 13:1011–1022.  https://doi.org/10.1089/ars.2009.2940 CrossRefGoogle Scholar
  17. Nicholls DG, Ferguson SJ (2013) 4 - the Chemiosmotic proton circuit in isolated organelles: theory and practice. In: Bioenergetics (4th edn). Academic Press, Boston, pp 53–87.  https://doi.org/10.1016/B978-0-12-388425-1.00004-X
  18. Palmer JW, Tandler B, Hoppel CL (1977) Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. J Biol Chem 252:8731–8739Google Scholar
  19. Paradies G, Paradies V, Ruggiero FM, Petrosillo G (2015) Cardiolipin alterations and mitochondrial dysfunction in heart ischemia/reperfusion injury. Clin Lipidol 10:415–429.  https://doi.org/10.2217/clp.15.31 CrossRefGoogle Scholar
  20. Picard M, White K, Turnbull DM (2013) Mitochondrial morphology, topology, and membrane interactions in skeletal muscle: a quantitative three-dimensional electron microscopy study. J Appl Physiol 114:161–171.  https://doi.org/10.1152/japplphysiol.01096.2012 CrossRefGoogle Scholar
  21. Ravindran S, Ansari Banu S, Kurian GA (2016) Hydrogen sulfide preconditioning shows differential protection towards interfibrillar and subsarcolemmal mitochondria from isolated rat heart subjected to revascularization injury. Cardiovasc Pathol 25:306–315.  https://doi.org/10.1016/j.carpath.2016.04.005 CrossRefGoogle Scholar
  22. Ravindran S, Boovarahan SR, Shanmugam K, Vedarathinam RC, Kurian GA (2017a) Sodium thiosulfate preconditioning ameliorates ischemia/reperfusion injury in rat hearts via reduction of oxidative stress and apoptosis. Cardiovasc Drugs Ther 31:511–524.  https://doi.org/10.1007/s10557-017-6751-0 CrossRefGoogle Scholar
  23. Ravindran S, Jahir Hussain S, Boovarahan SR, Kurian GA (2017b) Sodium thiosulfate post-conditioning protects rat hearts against ischemia reperfusion injury via reduction of apoptosis and oxidative stress. Chem Biol Interact 274:24–34.  https://doi.org/10.1016/j.cbi.2017.07.002 CrossRefGoogle Scholar
  24. Scaduto RC, Grotyohann LW (1999) Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys J 76:469–477CrossRefGoogle Scholar
  25. Sheeran FL, Pepe S (2006) Energy deficiency in the failing heart: linking increased reactive oxygen species and disruption of oxidative phosphorylation rate. Biochim Biophys Acta 1757:543–552.  https://doi.org/10.1016/j.bbabio.2006.03.008 CrossRefGoogle Scholar
  26. Siegel MP, Kruse SE, Knowels G, Salmon A, Beyer R, Xie H, van Remmen H, Smith SR, Marcinek DJ (2011) Reduced coupling of oxidative phosphorylation in vivo precedes electron transport chain defects due to mild oxidative stress in mice. PLoS One 6:e26963.  https://doi.org/10.1371/journal.pone.0026963 CrossRefGoogle Scholar
  27. Vanderlinde RE (1985) Measurement of total lactate dehydrogenase activity. Ann Clin Lab Sci 15:13–31Google Scholar
  28. Walters AM, Porter GA, Brookes PS (2012) Mitochondria as a drug target in ischemic heart disease and cardiomyopathy. Circ Res 111:1222–1236.  https://doi.org/10.1161/CIRCRESAHA.112.265660 CrossRefGoogle Scholar
  29. Wittig I, Karas M, Schagger H (2007) High resolution clear native electrophoresis for in-gel functional assays and fluorescence studies of membrane protein complexes. Mol Cell Proteomics 6:1215–1225.  https://doi.org/10.1074/mcp.M700076-MCP200 CrossRefGoogle Scholar
  30. Writing Group M et al (2017) Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation 135:e146–e603.  https://doi.org/10.1161/CIR.0000000000000485 Google Scholar
  31. Yu L, Gong B, Duan W, Fan C, Zhang J, Li Z, Xue X, Xu Y, Meng D, Li B, Zhang M, Bin Zhang, Jin Z, Yu S, Yang Y, Wang H (2017) Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling. Sci Rep 7:41337.  https://doi.org/10.1038/srep41337 CrossRefGoogle Scholar
  32. Zhu L, Wang Q, Zhang L, Fang Z, Zhao F, Lv Z, Gu Z, Zhang J, Wang J, Zen K, Xiang Y, Wang D, Zhang CY (2010) Hypoxia induces PGC-1alpha expression and mitochondrial biogenesis in the myocardium of TOF patients. Cell Res 20:676–687.  https://doi.org/10.1038/cr.2010.46 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Vascular Biology LabSASTRA-Deemed UniversityThanjavurIndia

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