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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
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
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
De Gubareff T, Furchgott RF (1956) The determination of inorganic phosphate and creatine phosphate in tissue extracts. J Biol Chem 223:377–388
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
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
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
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
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 88:529–535
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 70:68–78
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 31:5157–5166
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
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
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 960:62–70
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
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
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
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
Palmer JW, Tandler B, Hoppel CL (1977) Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. J Biol Chem 252:8731–8739
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
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
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
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
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
Scaduto RC, Grotyohann LW (1999) Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys J 76:469–477
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
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
Vanderlinde RE (1985) Measurement of total lactate dehydrogenase activity. Ann Clin Lab Sci 15:13–31
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
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
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
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
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
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 15 kb)
Rights and permissions
About this article
Cite this article
Ravindran, S., Kurian, G.A. Preconditioning the rat heart with sodium thiosulfate preserved the mitochondria in response to ischemia-reperfusion injury. J Bioenerg Biomembr 51, 189–201 (2019). https://doi.org/10.1007/s10863-019-09794-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10863-019-09794-8