Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 302, Issue 9, 2012, Pages

  Zang, Qun S ^a   Sadek, Hesham ^b   Maass, David L ^a   Martinez, Bobbie ^a   Ma, Lisha ^a   Kilgore, Jessica A ^a   Williams, Noelle S ^a   Frantz, Doug E ^a   Wigginton, Jane G ^a   Nwariaku, Fiemu E ^a   Wolf, Steven E ^a   Minei, Joseph P ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Heart failure; Mitochondria targeted antioxidants; Mitochondrial damage; Myocardial inflammation

Indexed keywords

ALPHA TOCOPHEROL; ALPHA TOCOPHEROL DERIVATIVE; CYTOCHROME C; INTERLEUKIN 1BETA; INTERLEUKIN 6; MITO VITAMIN E; MITOCHONDRIAL PROTEIN; MYELOPEROXIDASE; PROTECTIVE AGENT; REACTIVE OXYGEN METABOLITE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIOXIDANT ACTIVITY; ARTICLE; CONTROLLED STUDY; CYTOSOL; DRUG SYNTHESIS; ECHOCARDIOGRAPHY; HEART EJECTION FRACTION; HEART FUNCTION; HEART MITOCHONDRION; HEART MUSCLE CONTRACTILITY; HEART PROTECTION; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; LIPID PEROXIDATION; LYMPHOCYTIC INFILTRATION; MALE; MITOCHONDRIAL MEMBRANE; MYOCARDITIS; NONHUMAN; OXIDATIVE STRESS; PNEUMONIA; PRIORITY JOURNAL; RAT; RESPIRATORY FUNCTION; SEPSIS;

ANIMALS; ANTIOXIDANTS; CYTOKINES; DISEASE MODELS, ANIMAL; ECHOCARDIOGRAPHY; HEART; HYDROGEN PEROXIDE; INFLAMMATION; MALE; MITOCHONDRIA, HEART; MYOCARDIAL CONTRACTION; OXIDATIVE STRESS; PNEUMONIA, BACTERIAL; RATS; RATS, SPRAGUE-DAWLEY; REACTIVE OXYGEN SPECIES; SEPSIS; STREPTOCOCCUS PNEUMONIAE; VITAMIN E;

EID: 84860521449     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00203.2011     Document Type: Article

References (87)

1. Abel FL, Krosl P, Redl H. Beat-to-beat evaluation of cardiac function in low-dose endotoxemia using a conscious sheep model. Shock 16: 368-372, 2001.
2. Adlam VJ, Harrison JC, Porteous CM, James AM, Smith RA, Murphy MP, Sammut IA. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J 19: 1088-1095, 2005.
3. Akao M, O'Rourke B, Teshima Y, Seharaseyon J, Marban E. Mechanistically distinct steps in the mitochondrial death pathway triggered by oxidative stress in cardiac myocytes. Circ Res 92: 186-194, 2003.
4. Amstislavskaya TG, Maslova LN, Gladkikh DV, Belousova II, Stefanova NA, Kolosova NG. Effects of the mitochondria-targeted antioxidant SkQ1 on sexually motivated behavior in male rats. Pharmacol Biochem Behav 96: 211-216, 2010.
5. Andrades ME, Ritter C, Dal-Pizzol F. The role of free radicals in sepsis development. Front Biosci 1: 277-287, 2009.
6. Angstwurm MW, Engelmann L, Zimmermann T, Lehmann C, Spes CH, Abel P, Strauss R, Meier-Hellmann A, Insel R, Radke J, Schuttler J, Gartner R. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med 35: 118-126, 2007.
7. Angus DC, Pereira CA, Silva E. Epidemiology of severe sepsis around the world. Endocr Metab Immune Disord Drug Targets 6: 207-212, 2006.
8. Ballinger SW. Mitochondrial dysfunction in cardiovascular disease. Free Radic Biol Med 38: 1278-1295, 2005.
9. Bedard PM, Zweiman B, Atkins PC. Quantitation by myeloperoxidase assay of neutrophil accumulation at the site of in vivo allergic reactions. J Clin Immunol 3: 84-89, 1983.
10. Bell EL, Klimova TA, Eisenbart J, Moraes CT, Murphy MP, Budinger GR, Chandel NS. The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production. J Cell Biol 177: 1029-1036, 2007.
11. Berger MM, Chiolero RL. Antioxidant supplementation in sepsis and systemic inflammatory response syndrome. Crit Care Med 35: S584-S590, 2007.
12. Blanco J, Muriel-Bombin A, Sagredo V, Taboada F, Gandia F, Tamayo L, Collado J, Garcia-Labattut A, Carriedo D, Valledor M, De Frutos M, Lopez MJ, Caballero A, Guerra J, Alvarez B, Mayo A, Villar J. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care 12: R158, 2008.
13. Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360: 219-223, 2002.
14. Callahan LA, Supinski GS. Diaphragm and cardiac mitochondrial creatine kinases are impaired in sepsis. J Appl Physiol 102: 44-53, 2007.
15. Chacko BK, Reily C, Srivastava A, Johnson MS, Ye Y, Ulasova E, Agarwal A, Zinn KR, Murphy MP, Kalyanaraman B, Darley-Usmar V. Prevention of diabetic nephropathy in Ins2(+/)(AkitaJ) mice by the mitochondria-targeted therapy MitoQ. Biochem J 432: 9-19, 2010.
16. Chandran K, Aggarwal D, Migrino RQ, Joseph J, McAllister D, Konorev EA, Antholine WE, Zielonka J, Srinivasan S, Avadhani NG, Kalyanaraman B. Doxorubicin inactivates myocardial cytochrome c oxidase in rats: cardioprotection by Mito-Q. Biophys J 96: 1388-1398, 2009.
17. Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ. Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 278: 36027-36031, 2003.
18. Cocheme HM, Kelso GF, James AM, Ross MF, Trnka J, Mahendiran T, Asin-Cayuela J, Blaikie FH, Manas AR, Porteous CM, Adlam VJ, Smith RA, Murphy MP. Mitochondrial targeting of quinones: therapeutic implications. Mitochondrion 7, Suppl: S94-S102, 2007.
19. Coulter CV, Kelso GF, Lin TK, Smith RA, Murphy MP. Mitochondrially targeted antioxidants and thiol reagents. Free Radic Biol Med 28: 1547-1554, 2000.
20. Court O, Kumar A, Parrillo JE. Clinical review: myocardial depression in sepsis and septic shock. Crit Care 6: 500-508, 2002.
21. Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329: 23-38, 2003.
22. Demianenko IA, Vasilieva TV, Domnina LV, Dugina VB, Egorov MV, Ivanova OY, Ilinskaya OP, Pletjushkina OY, Popova EN, Sakharov IY, Fedorov AV, Chernyak BV. Novel mitochondria-targeted antioxidants, "Skulachev-ion" derivatives, accelerate dermal wound healing in animals. Biochemistry (Mosc) 75: 274-280, 2010.
23. Dhanasekaran A, Kotamraju S, Kalivendi SV, Matsunaga T, Shang T, Keszler A, Joseph J, Kalyanaraman B. Supplementation of endothelial cells with mitochondria-targeted antioxidants inhibit peroxide-induced mitochondrial iron uptake, oxidative damage, and apoptosis. J Biol Chem 279: 37575-37587, 2004.
24. Dhanasekaran A, Kotamraju S, Karunakaran C, Kalivendi SV, Thomas S, Joseph J, Kalyanaraman B. Mitochondria superoxide dismutase mimetic inhibits peroxide-induced oxidative damage and apoptosis: role of mitochondrial superoxide. Free Radic Biol Med 39: 567-583, 2005.
25. Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W, Harrison DG, Dikalov SI. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res 107: 106-116, 2010.
26. Doughan AK, Harrison DG, Dikalov SI. Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res 102: 488-496, 2008.
27. Fauconnier J, Meli AC, Thireau J, Roberge S, Shan J, Sassi Y, Reiken SR, Rauzier JM, Marchand A, Chauvier D, Cassan C, Crozier C, Bideaux P, Lompre AM, Jacotot E, Marks AR, Lacampagne A. Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion. Proc Natl Acad Sci U S A 108: 13258-13263, 2011.
28. Forceville X, Laviolle B, Annane D, Vitoux D, Bleichner G, Korach JM, Cantais E, Georges H, Soubirou JL, Combes A, Bellissant E. Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Crit Care 11: R73, 2007.
29. Galley HF. Bench-to-bedside review: targeting antioxidants to mitochondria in sepsis. Crit Care 14: 230, 2010.
30. Gane EJ, Weilert F, Orr DW, Keogh GF, Gibson M, Lockhart MM, Frampton CM, Taylor KM, Smith RA, Murphy MP. The mitochondria- targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver Int 30: 1019-1026, 2010.
31. Ghosh A, Chandran K, Kalivendi SV, Joseph J, Antholine WE, Hillard CJ, Kanthasamy A, Kanthasamy A, Kalyanaraman B. Neuroprotection by a mitochondria-targeted drug in a Parkinson's disease model. Free Radic Biol Med 49: 1674-1684, 2010.
32. Greenhalgh DG, Saffle JR, Holmes JH, Gamelli RL, Palmieri TL, Horton JW, Tompkins RG, Traber DL, Mozingo DW, Deitch EA, Goodwin CW, Herndon DN, Gallagher JJ, Sanford AP, Jeng JC, Ahrenholz DH, Neely AN, O'Mara MS, Wolf SE, Purdue GF, Garner WL, Yowler CJ, Latenser BA. American Burn Association consensus conference to define sepsis and infection in burns. J Burn Care Res 28: 776-790, 2007.
33. Gustafsson AB, Gottlieb RA. Heart mitochondria: gates of life and death. Cardiovasc Res 77: 334-343, 2008.
34. Han D, Williams E, Cadenas E. Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. Biochem J 353: 411-416, 2001.
35. Hollenberg SM, Dumasius A, Easington C, Colilla SA, Neumann A, Parrillo JE. Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography. Am J Respir Crit Care Med 164: 891-895, 2001.
36. Jauslin ML, Meier T, Smith RA, Murphy MP. Mitochondria-targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. FASEB J 17: 1972-1974, 2003.
37. Kapa S, Venkatachalam KL, Asirvatham SJ. The autonomic nervous system in cardiac electrophysiology: an elegant interaction and emerging concepts. Cardiol Rev 18: 275-284, 2010.
38. Kayar SR, Banchero N. Volume density and distribution of mitochondria in myocardial growth and hypertrophy. Respir Physiol 70: 275-286, 1987.
39. Kovacs A, Courtois MR, Barzilai B, Karl IE, Ludbrook PA, Hotchkiss RS. Reversal of hypocalcemia and decreased afterload in sepsis. Effect on myocardial systolic and diastolic function. Am J Respir Crit Care Med 158: 1990-1998, 1998.
40. Kunos G, Mucci L, O'Regan S. The influence of hormonal and neuronal factors on rat heart adrenoceptors. Br J Pharmacol 71: 371-386, 1980.
41. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, Parker MM, Gerlach H, Reinhart K, Silva E, Harvey M, Regan S, Angus DC. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 38: 367-374, 2010.
42. Levy RJ. Mitochondrial dysfunction, bioenergetic impairment, and metabolic down-regulation in sepsis. Shock 28: 24-28, 2007.
43. Long CL, Maull KI, Krishnan RS, Laws HL, Geiger JW, Borghesi L, Franks W, Lawson TC, Sauberlich HE. Ascorbic acid dynamics in the seriously ill and injured. J Surg Res 109: 144-148, 2003.
44. Lovat R, Preiser JC. Antioxidant therapy in intensive care. Curr Opin Crit Care 9: 266-270, 2003.
45. Lowes DA, Thottakam BM, Webster NR, Murphy MP, Galley HF. The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis. Free Radic Biol Med 45: 1559-1565, 2008.
46. Lowes DA, Wallace C, Murphy MP, Webster NR, Galley HF. The mitochondria targeted antioxidant MitoQ protects against fluoroquinoloneinduced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells. Free Radic Res 43: 323-328, 2009.
47. Manczak M, Mao P, Calkins MJ, Cornea A, Reddy AP, Murphy MP, Szeto HH, Park B, Reddy PH. Mitochondria-targeted antioxidants protect against amyloid-beta toxicity in Alzheimer's disease neurons. J Alzheimers Dis 20, Suppl 2: S609-S631, 2010.
48. Matsushita A, Iwase M, Kato Y, Ichihara S, Ichihara G, Kimata H, Hayashi K, Hashimoto K, Yokoi T, Noda A, Koike Y, Yokota M, Nagata K. Differential cardiovascular effects of endotoxin derived from Escherichia coli or Pseudomonas aeruginosa. Exp Anim 56: 339-348, 2007.
49. Moorman JR, Lake DE, Griffin MP. Heart rate characteristics monitoring for neonatal sepsis. IEEE Trans Biomed Eng 53: 126-132, 2006.
50. Morten KJ, Ackrell BA, Melov S. Mitochondrial reactive oxygen species in mice lacking superoxide dismutase 2: attenuation via antioxidant treatment. J Biol Chem 281: 3354-3359, 2006.
51. Murphy MP, Smith RA. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu Rev Pharmacol Toxicol 47: 629-656, 2007.
52. Musatov A, Ortega-Lopez J, Robinson NC. Detergent-solubilized bovine cytochrome c oxidase: dimerization depends on the amphiphilic environment. Biochemistry 39: 12996-13004, 2000.
53. O'Brien JM Jr, Ali NA, Aberegg SK, Abraham E. Sepsis. Am J Med 120: 1012-1022, 2007.
54. Okaya T, Blanchard J, Schuster R, Kuboki S, Husted T, Caldwell CC, Zingarelli B, Wong H, Solomkin JS, Lentsch AB. Age-dependent responses to hepatic ischemia/reperfusion injury. Shock 24: 421-427, 2005.
55. Parrillo JE, Parker MM, Natanson C, Suffredini AF, Danner RL, Cunnion RE, Ognibene FP. Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med 113: 227-242, 1990.
56. Paterson RL, Galley HF, Webster NR. The effect of N-acetylcysteine on nuclear factor-kappa B activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis. Crit Care Med 31: 2574-2578, 2003.
57. Porteous CM, Logan A, Evans C, Ledgerwood EC, Menon DK, Aigbirhio F, Smith RA, Murphy MP. Rapid uptake of lipophilic triphenylphosphonium cations by mitochondria in vivo following intravenous injection: implications for mitochondria-specific therapies and probes. Biochim Biophys Acta 1800: 1009-1017, 2010.
58. Reynolds CM, Suliman HB, Hollingsworth JW, Welty-Wolf KE, Carraway MS, Piantadosi CA. Nitric oxide synthase-2 induction optimizes cardiac mitochondrial biogenesis after endotoxemia. Free Radic Biol Med 46: 564-572, 2009.
59. Rinaldi S, Landucci F, De Gaudio AR. Antioxidant therapy in critically septic patients. Curr Drug Targets 10: 872-880, 2009.
60. Ritter C, Andrades ME, Reinke A, Menna-Barreto S, Moreira JC, Dal-Pizzol F. Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Crit Care Med 32: 342-349, 2004.
61. Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med 35: 1599-1608, 2007.
62. Sadek H, Hannack B, Choe E, Wang J, Latif S, Garry MG, Garry DJ, Longgood J, Frantz DE, Olson EN, Hsieh J, Schneider JW. Cardiogenic small molecules that enhance myocardial repair by stem cells. Proc Natl Acad Sci U S A 105: 6063-6068, 2008.
63. Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P. Toxic proteins released from mitochondria in cell death. Oncogene 23: 2861-2874, 2004.
64. Schierwagen C, Bylund-Fellenius AC, Lundberg C. Improved method for quantification of tissue PMN accumulation measured by myeloperoxidase activity. J Pharmacol Methods 23: 179-186, 1990.
65. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NFkappaB and IRF 3. Cell 122: 669-682, 2005.
66. Sheeran PW, Maass DL, White DJ, Turbeville TD, Giroir BP, Horton JW. Aspiration pneumonia-induced sepsis increases cardiac dysfunction after burn trauma. J Surg Res 76: 192-199, 1998.
67. Singer M. Mitochondrial function in sepsis: acute phase versus multiple organ failure. Crit Care Med 35: S441-S448, 2007.
68. Smith RA, Porteous CM, Gane AM, Murphy MP. Delivery of bioactive molecules to mitochondria in vivo. Proc Natl Acad Sci U S A 100: 5407-5412, 2003.
69. Supinski GS, Murphy MP, Callahan LA. MitoQ administration prevents endotoxin-induced cardiac dysfunction. Am J Physiol Regul Integr Comp Physiol 297: R1095-R1102, 2009.
70. Szeto HH. Cell-permeable, mitochondrial-targeted, peptide antioxidants. AAPS J 8: E277-E283, 2006.
71. Szeto HH. Mitochondria-targeted cytoprotective peptides for ischemiareperfusion injury. Antioxid Redox Signal 10: 601-619, 2008.
72. Tao W, Maass DL, Johnston WE, Horton JW. Murine in vivo myocardial contractile dysfunction after burn injury is exacerbated by pneumonia sepsis. Shock 24: 495-499, 2005.
73. Tsutsui H, Kinugawa S, Matsushima S. Oxidative stress and mitochondrial DNA damage in heart failure. Circulation journal: official journal of the Japanese Circulation Society 72, Suppl A: A31-A37, 2008.
74. von Dessauer B, Bongain J, Molina V, Quilodran J, Castillo R, Rodrigo R. Oxidative stress as a novel target in pediatric sepsis management. J Crit Care 26: 103 e101-e107, 2011.
75. Wang L, Quan J, Johnston WE, Maass DL, Horton JW, Thomas JA, Tao W. Age-dependent differences of interleukin-6 activity in cardiac function after burn complicated by sepsis. Burns 36: 232-238, 2010.
76. Wang Y, Zang QS, Liu Z, Wu Q, Maass D, Dulan G, Shaul PW, Melito L, Frantz DE, Kilgore JA, Williams NS, Terada LS, Nwariaku FE. Regulation of VEGF induced endothelial cell migration by mitochondrial reactive oxygen species. Am J Physiol Cell Physiol 301: C695-C704, 2011.
77. Watts JA, Kline JA, Thornton LR, Grattan RM, Brar SS. Metabolic dysfunction and depletion of mitochondria in hearts of septic rats. J Mol Cell Cardiol 36: 141-150, 2004.
78. White J, Thomas J, Maass DL, Horton JW. Cardiac effects of burn injury complicated by aspiration pneumonia-induced sepsis. Am J Physiol Heart Circ Physiol 285: H47-H58, 2003.
79. Wojtczak L, Zaluska H, Wroniszewska A, Wojtczak AB. Assay for the intactness of the outer membrane in isolated mitochondria. Acta Biochim Pol 19: 227-234, 1972.
80. Zang Q, Maass DL, Tsai SJ, Horton JW. Cardiac mitochondrial damage and inflammation responses in sepsis. Surg Infect (Larchmt) 8: 41-54, 2007.
81. Zang Q, Maass DL, White J, Horton JW. Cardiac mitochondrial damage and loss of ROS defense after burn injury: the beneficial effects of antioxidant therapy. J Appl Physiol 102: 103-112, 2007.
82. Zanotti-Cavazzoni SL, Guglielmi M, Parrillo JE, Walker T, Dellinger RP, Hollenberg SM. Fluid resuscitation influences cardiovascular performance and mortality in a murine model of sepsis. Intensive Care Med 35: 748-754, 2009.
83. Zanotti-Cavazzoni SL, Hollenberg SM. Cardiac dysfunction in severe sepsis and septic shock. Curr Opin Crit Care 15: 392-397, 2009.
84. Zhang Q, Itagaki K, Hauser CJ. Mitochondrial DNA is released by shock and activates neutrophils via p38 MAP-kinase. Shock 34: 55-59, 2010.
85. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464: 104-107, 2010.
86. Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW, Szeto HH. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem 279: 34682-34690, 2004.
87. Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469: 221-225, 2011.