Journal of Molecular and Cellular Cardiology
Volume 49, Issue 5 , Pages 746-752 , November 2010

HIV protease inhibitors elicit volume-sensitive Cl current in cardiac myocytes via mitochondrial ROS

  • Wu Deng

      Affiliations

    • Department of Physiology and Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
  • ,
  • Lia Baki

      Affiliations

    • Department of Physiology and Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
  • ,
  • Jun Yin

      Affiliations

    • Departments of Internal Medicine (Cardiology), Virginia Commonwealth University, Richmond, VA 23298, USA
  • ,
  • Huiping Zhou

      Affiliations

    • Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA
  • ,
  • Clive M. Baumgarten

      Affiliations

    • Department of Physiology and Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
    • Departments of Internal Medicine (Cardiology), Virginia Commonwealth University, Richmond, VA 23298, USA
    • Corresponding Author InformationCorresponding author. Dept. of Physiology & Biophysics, Virginia Commonwealth Univ., 1101 E. Marshall St., Richmond, VA 23298-0551, USA. Tel.: +1 804 828 4773; fax: +1 804 828 7382.

Received 22 September 2009 ,Revised 26 July 2010 ,Accepted 13 August 2010.

References 

  1. Flint OP, Noor MA, Hruz PW, Hylemon PB, Yarasheski K, Kotler DP, et al. The role of protease inhibitors in the pathogenesis of HIV-associated lipodystrophy: cellular mechanisms and clinical implications. Toxicol Pathol. 2009;37:65–77
  2. Anson BD, Weaver JG, Ackerman MJ, Akinsete O, Henry K, January CT, et al. Blockade of HERG channels by HIV protease inhibitors. Lancet. 2005;365:682–686
  3. Busti AJ, Tsikouris JP, Peeters MJ, Das SR, Canham RM, Abdullah SM, et al. A prospective evaluation of the effect of atazanavir on the QTc interval and QTc dispersion in HIV-positive patients. HIV Med. 2006;7:317–322
  4. Chinello P, Lisena FP, Angeletti C, Boumis E, Papetti F, Petrosillo N. Role of antiretroviral treatment in prolonging QTc interval in HIV-positive patients. J Infect. 2007;54:597–602
  5. Fiala M, Murphy T, MacDougall J, Yang W, Luque A, Iruela-Arispe L, et al. HAART drugs induce mitochondrial damage and intercellular gaps and gp120 causes apoptosis. Cardiovasc Toxicol. 2004;4:327–337
  6. Hruz PW, Yan Q, Struthers H, Jay PY. HIV protease inhibitors that block GLUT4 precipitate acute, decompensated heart failure in a mouse model of dilated cardiomyopathy. FASEB J. 2008;22:2161–2167
  7. McArthur MA, Kalu SU, Foulks AR, Aly AM, Jain SK, Patel JA. Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy. Pediatr Infect Dis J. 2009;28:1127–1129
  8. Conklin BS, Fu W, Lin PH, Lumsden AB, Yao Q, Chen C. HIV protease inhibitor ritonavir decreases endothelium-dependent vasorelaxation and increases superoxide in porcine arteries. Cardiovasc Res. 2004;63:168–175
  9. Chai H, Yang H, Yan S, Li M, Lin PH, Lumsden AB, et al. Effects of 5 HIV protease inhibitors on vasomotor function and superoxide anion production in porcine coronary arteries. J Acquir Immune Defic Syndr. 2005;40:12–19
  10. Rudich A, Ben-Romano R, Etzion S, Bashan N. Cellular mechanisms of insulin resistance, lipodystrophy and atherosclerosis induced by HIV protease inhibitors. Acta Physiol Scand. 2005;183:75–88
  11. Jiang B, Hebert VY, Li Y, Mathis JM, Alexander JS, Dugas TR. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis. Toxicol Appl Pharmacol. 2007;224:60–71
  12. Wang X, Chai H, Lin PH, Yao Q, Chen C. Roles and mechanisms of human immunodeficiency virus protease inhibitor ritonavir and other anti-human immunodeficiency virus drugs in endothelial dysfunction of porcine pulmonary arteries and human pulmonary artery endothelial cells. Am J Pathol. 2009;174:771–781
  13. Ben-Romano R, Rudich A, Etzion S, Potashnik R, Kagan E, Greenbaum U, et al. Nelfinavir induces adipocyte insulin resistance through the induction of oxidative stress: differential protective effect of antioxidant agents. Antivir Ther. 2006;11:1051–1060
  14. Lagathu C, Eustace B, Prot M, Frantz D, Gu Y, Bastard JP, et al. Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages. Antivir Ther. 2007;12:489–500
  15. Wang X, Mu H, Chai H, Liao D, Yao Q, Chen C. Human immunodeficiency virus protease inhibitor ritonavir inhibits cholesterol efflux from human macrophage-derived foam cells. Am J Pathol. 2007;171:304–314
  16. Caron M, Auclair M, Donadille B, Bereziat V, Guerci B, Laville M, et al. Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence. Cell Death Differ. 2007;14:1759–1767
  17. Chandra S, Mondal D, Agrawal KC. HIV-1 protease inhibitor induced oxidative stress suppresses glucose stimulated insulin release: protection with thymoquinone. Exp Biol Med (Maywood ). 2009;234:442–453
  18. Viengchareun S, Caron M, Auclair M, Kim MJ, Frachon P, Capeau J, et al. Mitochondrial toxicity of indinavir, stavudine and zidovudine involves multiple cellular targets in white and brown adipocytes. Antivir Ther. 2007;12:919–929
  19. Browe DM, Baumgarten CM. Angiotensin II (AT1) receptors and NADPH oxidase regulate Cl- current elicited by β1 integrin stretch in rabbit ventricular myocytes. J Gen Physiol. 2004;124:273–287
  20. Browe DM, Baumgarten CM. EGFR kinase regulates volume-sensitive chloride current elicited by integrin stretch via PI-3K and NADPH oxidase in ventricular myocytes. J Gen Physiol. 2006;127:237–251
  21. Ren Z, Raucci FJ, Browe DM, Baumgarten CM. Regulation of swelling-activated Cl current by angiotensin II signalling and NADPH oxidase in rabbit ventricle. Cardiovasc Res. 2008;77:73–80
  22. Varela D, Simon F, Riveros A, Jorgensen F, Stutzin A. NAD(P)H oxidase-derived H2O2 signals chloride channel activation in cell volume regulation and cell proliferation. J Biol Chem. 2004;279:13301–13304
  23. Shimizu T, Numata T, Okada Y. A role of reactive oxygen species in apoptotic activation of volume-sensitive Cl channel. Proc Natl Acad Sci USA. 2004;101:6770–6773
  24. Haskew-Layton RE, Mongin AA, Kimelberg HK. Hydrogen peroxide potentiates volume-sensitive excitatory amino acid release via a mechanism involving Ca2+/calmodulin-dependent protein kinase II. J Biol Chem. 2005;280:3548–3554
  25. Deng W, Baki L, Baumgarten CM. Endothelin signaling regulates volume-sensitive Cl current via NADPH oxidase and mitochondrial reactive oxygen species. Cardiovasc Res. 2010;[Epub ahead of print]
  26. Decher N, Lang HJ, Nilius B, Bruggemann A, Busch AE, Steinmeyer K. DCPIB is a novel selective blocker of ICl, swell and prevents swelling-induced shortening of guinea-pig action potential duration. Br J Pharmacol. 2001;134:1467–1479
  27. Ximenes VF, Kanegae MP, Rissato SR, Galhiane MS. The oxidation of apocynin catalyzed by myeloperoxidase: proposal for NADPH oxidase inhibition. Arch Biochem Biophys. 2007;457:134–141
  28. 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. 2003;278:36027–36031
  29. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552:335–344
  30. Tarpey MM, Wink DA, Grisham MB. Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations. Am J Physiol Regul Integr Comp Physiol. 2004;286:R431–R444
  31. Deng W, Raucci FJ, Baki L, Baumgarten CM. Regulation of volume-sensitive chloride current in cardiac HL-1 myocytes. Biophys J. 2010;98(Suppl 1):338a;(Abstract)
  32. Muller FL, Liu Y, Van RH. Complex III releases superoxide to both sides of the inner mitochondrial membrane. J Biol Chem. 2004;279:49064–49073
  33. Aon MA, Cortassa S, Marban E, O'Rourke B. Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes. J Biol Chem. 2003;278:44735–44744
  34. Mondal D, Pradhan L, Ali M, Agrawal KC. HAART drugs induce oxidative stress in human endothelial cells and increase endothelial recruitment of mononuclear cells: exacerbation by inflammatory cytokines and amelioration by antioxidants. Cardiovasc Toxicol. 2004;4:287–302
  35. Grigorian A, Hurford R, Chao Y, Patrick C, Langford TD. Alterations in the Notch4 pathway in cerebral endothelial cells by the HIV aspartyl protease inhibitor, nelfinavir. BMC Neurosci. 2008;9:27
  36. Vincent S, Tourniaire F, El Yazidi CM, Compe E, Manches O, Plannels R, et al. Nelfinavir induces necrosis of 3T3F44-2A adipocytes by oxidative stress. J Acquir Immune Defic Syndr. 2004;37:1556–1562
  37. Lekakis J, Tsiodras S, Ikonomidis I, Palios J, Poulakou G, Rallidis L, et al. HIV-positive patients treated with protease inhibitors have vascular changes resembling those observed in atherosclerotic cardiovascular disease. Clin Sci (Lond). 2008;115:189–196
  38. Vaughn G, Detels R. Protease inhibitors and cardiovascular disease: analysis of the Los Angeles County adult spectrum of disease cohort. AIDS Care. 2007;19:492–499
  39. Roden DM. Cellular basis of drug-induced torsades de pointes. Br J Pharmacol. 2008;154:1502–1507
  40. Song Y, Shryock JC, Wagner S, Maier LS, Belardinelli L. Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction. J Pharmacol Exp Ther. 2006;318:214–222
  41. Zima AV, Blatter LA. Redox regulation of cardiac calcium channels and transporters. Cardiovasc Res. 2006;71:310–321

PII: S0022-2828(10)00300-7

doi: 10.1016/j.yjmcc.2010.08.013

Journal of Molecular and Cellular Cardiology
Volume 49, Issue 5 , Pages 746-752 , November 2010