DOI QR코드

DOI QR Code

Inhibiting Cytochrome C Oxidase Leads to Alleviated Ischemia Reperfusion Injury

  • Yang, Zhaoyun (Department of Anesthesia, Xiang-Ya Second Hospital, Central South University) ;
  • Duan, Zhongxin (Department of Anesthesiology, the Second Affiliated Hospital, University of South China) ;
  • Yu, Tian (Department of Anesthesiology, Zunyi Medical College) ;
  • Xu, Junmei (Department of Anesthesia, Xiang-Ya Second Hospital, Central South University) ;
  • Liu, Lei (Department of Anesthesia, Xiang-Ya Second Hospital, Central South University)
  • Received : 2016.03.28
  • Accepted : 2016.07.07
  • Published : 2017.03.31

Abstract

Background and Objectives: The overall purpose of this study was to investigate the role of cytochrome C oxidase (CcO) in preventing ischemia reperfusion-induced cardiac injury through gaseous signaling molecule pathways. Materials and Methods: We used CcO inhibitor, potassium cyanide (KCN) to mimic the pre-treatment of gaseous signaling molecules in a global ischemia/reperfusion (IR) injury model in rats. Intracellular reactive oxygen species (ROS) was determined by measuring mitochondrial $H_2O_2$ and mitochondrial complex activity. Results: KCN pre-treatment led to decreased infarction area after IR injury and improved cardiac function. KCN pre-treated group challenged with IR injury was associated with reduced ROS production through inhibition of activity and not downregulation of CcO expression. In addition, KCN pre-treatment was associated with enhanced expression and activity of mitochondrial antioxidase, suggesting the role of CcO in regulating IR injury through oxidative stress. Conclusion: KCN pre-treatment reduced the severity of IR injury. The potential mechanism could be increased endogenous anti-oxidase activity and consequently, the enhanced clearance of ROS.

Keywords

Acknowledgement

Supported by : National Natural Science Foundation of China

References

  1. Tsukihara T, Aoyama H, Yamashita E, et al. Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A. Science 1995;269:1069-74. https://doi.org/10.1126/science.7652554
  2. Huttemann M, Helling S, Sanderson TH, et al. Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation. Biochim Biophys Acta 2012;1817:598-609. https://doi.org/10.1016/j.bbabio.2011.07.001
  3. Groening P, Huang Z, La Gamma EF, Levy RJ. Glutamine restores myocardial cytochrome C oxidase activity and improves cardiac function during experimental sepsis. JPEN J Parenter Enteral Nutr 2011;35:249-54. https://doi.org/10.1177/0148607110383040
  4. Bruno C, Martinuzzi A, Tang Y, et al. A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV. Am J Hum Genet 1999;65:611-20. https://doi.org/10.1086/302546
  5. Comi GP, Bordoni A, Salani S, et al. Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. Ann Neurol 1998;43:110-6. https://doi.org/10.1002/ana.410430119
  6. Muller-Hocker J. Cytochrome-c-oxidase deficient cardiomyocytes in the human heart--an age-related phenomenon. A histochemical ultracytochemical study. Am J Pathol 1989;134:1167-73.
  7. Antonicka H, Mattman A, Carlson CG, et al. Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy. Am J Hum Genet 2003;72:101-14. https://doi.org/10.1086/345489
  8. Papadopoulou LC, Sue CM, Davidson MM, et al. Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. Nat Genet 1999;23:333-7. https://doi.org/10.1038/15513
  9. Prabu SK, Anandatheerthavarada HK, Raza H, Srinivasan S, Spear JF, Avadhani NG. Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function and augments hypoxia and myocardial ischemia-related injury. J Biol Chem 2006;281:2061-70. https://doi.org/10.1074/jbc.M507741200
  10. Booth EA, Flint RR, Lucas KL, Knittel AK, Lucchesi BR. Estrogen protects the heart from ischemia-reperfusion injury via COX-2- derived PGI2. J Cardiovasc Pharmacol 2008;52:228-35. https://doi.org/10.1097/FJC.0b013e3181824d59
  11. Vogt S, Ramzan R, Weber P, et al. Ischemic preconditioning results in an ATP-dependent inhibition of cytochrome C oxidase. Shock 2013;40;407-13. https://doi.org/10.1097/SHK.0b013e3182a51a06
  12. Sun WH, Liu F, Chen Y, Zhu YC. Hydrogen sulfide decreases the levels of ROS by inhibiting mitochondrial complex IV and increasing SOD activities in cardiomyocytes under ischemia/reperfusion. Biochem Biophys Res Commun 2012;421:164-9. https://doi.org/10.1016/j.bbrc.2012.03.121
  13. Whittington HJ, Hall AR, McLaughlin CP, Hausenloy DJ, Yellon DM, Mocanu MM. Chronic metformin associated cardioprotection against infarction: not just a glucose lowering phenomenon. Cardiovasc Drugs Ther 2013;27:5-16. https://doi.org/10.1007/s10557-012-6425-x
  14. Burkard N, Williams T, Czolbe M, et al. Conditional overexpression of neuronal nitric oxide synthase is cardioprotective in ischemia/ reperfusion. Circulation 2010;122:1588-603. https://doi.org/10.1161/CIRCULATIONAHA.109.933630
  15. Guo W, Cheng ZY, Zhu YZ. Hydrogen sulfide and translational medicine. Acta Pharmacol Sin 2013;34:1284-91. https://doi.org/10.1038/aps.2013.127
  16. Zuckerbraun BS, Chin BY, Bilban M, et al. Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species. FASEB J 2007;21:1099-106. https://doi.org/10.1096/fj.06-6644com
  17. Jain M, Rivera S, Monclus EA, et al. Mitochondrial reactive oxygen species regulate transforming growth factor-beta signaling. J Biol Chem 2013;288:770-7. https://doi.org/10.1074/jbc.M112.431973
  18. Diaz F. Cytochrome c oxidase deficiency: patients and animal models. Biochim Biophys Acta 2010;1802:100-10. https://doi.org/10.1016/j.bbadis.2009.07.013
  19. Nicholson CK, Calvert JW. Hydrogen sulfide and ischemia-reperfusion injury. Pharmacol Res 2010;62;289-97. https://doi.org/10.1016/j.phrs.2010.06.002
  20. Chen Q, Camara AK, Stowe DF, Hoppel CL, Lesnefsky EJ. Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion. Am J Physiol Cell Physiol 2007;292:C137-47. https://doi.org/10.1152/ajpcell.00270.2006
  21. Tanaka-Esposito C, Chen Q, Lesnefsky EJ. Blockade of electron transport before ischemia protects mitochondria and decreases myocardial injury during reperfusion in aged rat hearts. Transl Res 2012;160:207-16. https://doi.org/10.1016/j.trsl.2012.01.024

Cited by

  1. The Effects of Potassium Cyanide on the Functional Recovery of Isolated Rat Hearts after Ischemia and Reperfusion: The Role of Oxidative Stress vol.2018, pp.None, 2018, https://doi.org/10.1155/2018/5979721
  2. Sirt1 Activation by Post-ischemic Treatment With Lumbrokinase Protects Against Myocardial Ischemia-Reperfusion Injury vol.9, pp.None, 2017, https://doi.org/10.3389/fphar.2018.00636