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Open Access 01-09-2014 | Original Contribution

S-nitrosation of mitochondrial connexin 43 regulates mitochondrial function

Authors: Daniel Soetkamp, Tiffany T. Nguyen, Sara Menazza, Christine Hirschhäuser, Ulrike B. Hendgen-Cotta, Tienush Rassaf, Klaus D. Schlüter, Kerstin Boengler, Elizabeth Murphy, Rainer Schulz

Published in: Basic Research in Cardiology | Issue 5/2014

Abstract

S-nitrosation (SNO) of connexin 43 (Cx43)-formed channels modifies dye uptake in astrocytes and gap junctional communication in endothelial cells. Apart from forming channels at the plasma membrane of several cell types, Cx43 is also located at the inner membrane of myocardial subsarcolemmal mitochondria (SSM), but not in interfibrillar mitochondria (IFM). The absence or pharmacological blockade of mitochondrial Cx43 (mtCx43) reduces dye and potassium uptake. Lack of mtCx43 is associated with loss of endogenous cardioprotection by ischemic preconditioning (IPC), which is mediated by formation of reactive oxygen species (ROS). Whether or not mitochondrial Lucifer Yellow (LY), ion uptake, or ROS generation are affected by SNO of mtCx43 and whether or not cardioprotective interventions affect SNO of mtCx43 remains unknown. In SSM from rat hearts, application of NO donors (48 nmol to 1 mmol) increased LY uptake (0.5 mmol SNAP 38.4 ± 7.1 %, p < 0.05; 1 mmol GSNO 28.1 ± 7.4 %, p < 0.05) and the refilling rate of potassium (SNAP 227.9 ± 30.1 %, p < 0.05; GSNO 122.6 ± 28.1 %, p < 0.05). These effects were absent following blockade of Cx43 hemichannels by carbenoxolone as well as in IFM lacking Cx43. Unlike potassium, the sodium permeability was not affected by application of NO. Furthermore, mitochondrial ROS formation was increased following NO application compared to control SSM (0.5 mmol SNAP 22.9 ± 1.8 %, p < 0.05; 1 mmol GSNO 40.6 ± 7.1 %, p < 0.05), but decreased in NO treated IFM compared to control (0.5 mmol SNAP 14.4 ± 4 %, p < 0.05; 1 mmol GSNO 13.8 ± 4 %, p < 0.05). NO donor administration to isolated SSM increased SNO of mtCx43 by 109.2 ± 15.8 %. Nitrite application (48 nmol) to mice was also associated with elevated SNO of mtCx43 by 59.3 ± 18.2 % (p < 0.05). IPC by four cycles of 5 min of ischemia and 5 min of reperfusion increased SNO of mtCx43 by 41.6 ± 1.7 % (p < 0.05) when compared to control perfused rat hearts. These data suggest that SNO of mtCx43 increases mitochondrial permeability, especially for potassium and leads to increased ROS formation. The increased amount of SNO mtCx43 by IPC or nitrite administration may link NO and Cx43 in the signal transduction cascade of cardioprotective interventions.

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Boengler K, Dodoni G, Rodriguez-Sinovas A, Cabestrero A, Ruiz-Meana M, Gres P, Konietzka I, Lopez-Iglesias C, Garcia-Dorado D, Di Lisa F, Heusch G, Schulz R (2005) Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res 67:234–244. doi:10.1016/j.cardiores.2005.04.014 PubMedCrossRef

Boengler K, Ruiz-Meana M, Gent S, Ungefug E, Soetkamp D, Miro-Casas E, Cabestrero A, Fernandez-Sanz C, Semenzato M, Di Lisa F, Rohrbach S, Garcia-Dorado D, Heusch G, Schulz R (2012) Mitochondrial connexin 43 impacts on respiratory complex I activity and mitochondrial oxygen consumption. J Cell Mol Med 16:1649–1655. doi:10.1111/j.1582-4934.2011.01516.x PubMedCrossRef

Boengler K, Schulz R, Heusch G (2006) Connexin 43 signalling and cardioprotection. Heart 92:1724–1727. doi:10.1136/hrt.2005.066878 PubMedCrossRefPubMedCentral

Boengler K, Stahlhofen S, van de Sand A, Gres P, Ruiz-Meana M, Garcia-Dorado D, Heusch G, Schulz R (2009) Presence of connexin 43 in subsarcolemmal, but not in interfibrillar cardiomyocyte mitochondria. Basic Res Cardiol 104:141–147. doi:10.1007/s00395-009-0007-5 PubMedCrossRef

Boengler K, Ungefug E, Heusch G, Leybaert L, Schulz R (2013) Connexin 43 impacts on mitochondrial potassium uptake. Front Pharmacol 4:73. doi:10.3389/fphar.2013.00073 PubMedCrossRefPubMedCentral

Chai YC, Hendrich S, Thomas JA (1994) Protein S-thiolation in hepatocytes stimulated by t-butyl hydroperoxide, menadione, and neutrophils. Arch Biochem Biophys 310:264–272. doi:10.1006/abbi.1994.1166 PubMedCrossRef

Chouchani ET, Methner C, Nadtochiy SM, Logan A, Pell VR, Ding S, James AM, Cocheme HM, Reinhold J, Lilley KS, Partridge L, Fearnley IM, Robinson AJ, Hartley RC, Smith RA, Krieg T, Brookes PS, Murphy MP (2013) Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med 19:753–759. doi:10.1038/nm.3212 PubMedCrossRefPubMedCentral

Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon RO 3rd, Gladwin MT (2003) Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 9:1498–1505. doi:10.1038/nm954 PubMedCrossRef

10.

Davidson JS, Baumgarten IM (1988) Glycyrrhetinic acid derivatives: a novel class of inhibitors of gap-junctional intercellular communication. Structure–activity relationships. J Pharmacol Exp Ther 246:1104–1107PubMed

11.

Davidson JS, Baumgarten IM, Harley EH (1986) Reversible inhibition of intercellular junctional communication by glycyrrhetinic acid. Biochem Biophys Res Commun 134:29–36PubMedCrossRef

12.

De Vuyst E, Boengler K, Antoons G, Sipido KR, Schulz R, Leybaert L (2011) Pharmacological modulation of connexin-formed channels in cardiac pathophysiology. Br J Pharmacol 163:469–483. doi:10.1111/j.1476-5381.2011.01244.x PubMedCrossRefPubMedCentral

13.

Donoso P, Mill JG, O’Neill SC, Eisner DA (1992) Fluorescence measurements of cytoplasmic and mitochondrial sodium concentration in rat ventricular myocytes. J Physiol 448:493–509PubMedPubMedCentral

14.

Dutka TL, Mollica JP, Posterino GS, Lamb GD (2011) Modulation of contractile apparatus Ca2+ sensitivity and disruption of excitation-contraction coupling by S-nitrosoglutathione in rat muscle fibres. J Physiol 589:2181–2196. doi:10.1113/jphysiol.2010.200451 PubMedCrossRefPubMedCentral

15.

Espey MG, Miranda KM, Thomas DD, Xavier S, Citrin D, Vitek MP, Wink DA (2002) A chemical perspective on the interplay between NO, reactive oxygen species, and reactive nitrogen oxide species. Ann N Y Acad Sci 962:195–206PubMedCrossRef

16.

Gao S, Chen J, Brodsky SV, Huang H, Adler S, Lee JH, Dhadwal N, Cohen-Gould L, Gross SS, Goligorsky MS (2004) Docking of endothelial nitric oxide synthase (eNOS) to the mitochondrial outer membrane: a pentabasic amino acid sequence in the autoinhibitory domain of eNOS targets a proteinase K-cleavable peptide on the cytoplasmic face of mitochondria. J Biol Chem 279:15968–15974. doi:10.1074/jbc.M308504200 PubMedCrossRef

17.

Giustarini D, Milzani A, Dalle-Donne I, Rossi R (2007) Detection of S-nitrosothiols in biological fluids: a comparison among the most widely applied methodologies. J Chromatogr B Analyt Technol Biomed Life Sci 851:124–139. doi:10.1016/j.jchromb.2006.09.031 PubMedCrossRef

18.

Gonzalez DR, Beigi F, Treuer AV, Hare JM (2007) Deficient ryanodine receptor S-nitrosylation increases sarcoplasmic reticulum calcium leak and arrhythmogenesis in cardiomyocytes. Proc Natl Acad Sci USA 104:20612–20617. doi:10.1073/pnas.0706796104 PubMedCrossRefPubMedCentral

19.

Goodenough DA, Paul DL (2003) Beyond the gap: functions of unpaired connexon channels. Nat Rev Mol Cell Biol 4:285–294. doi:10.1038/nrm1072 PubMedCrossRef

20.

Hansford RG, Hogue BA, Mildaziene V (1997) Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age. J Bioenerg Biomembr 29:89–95PubMedCrossRef

21.

Hare JM (2003) Nitric oxide and excitation-contraction coupling. J Mol Cell Cardiol 35:719–729PubMedCrossRef

22.

Hausenloy DJ, Maddock HL, Baxter GF, Yellon DM (2002) Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res 55:534–543PubMedCrossRef

23.

Heinzel FR, Luo Y, Li X, Boengler K, Buechert A, Garcia-Dorado D, Di Lisa F, Schulz R, Heusch G (2005) Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice. Circ Res 97:583–586. doi:10.1161/01.RES.0000181171.65293.65 PubMedCrossRef

24.

Heusch G, Boengler K, Schulz R (2008) Cardioprotection: nitric oxide, protein kinases, and mitochondria. Circulation 118:1915–1919. doi:10.1161/CIRCULATIONAHA.108.805242 PubMedCrossRef

25.

Heytler PG (1979) Uncouplers of oxidative phosphorylation. Methods Enzymol 55:442–462

26.

Iwakiri Y, Satoh A, Chatterjee S, Toomre DK, Chalouni CM, Fulton D, Groszmann RJ, Shah VH, Sessa WC (2006) Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking. Proc Natl Acad Sci USA 103:19777–19782. doi:10.1073/pnas.0605907103 PubMedCrossRefPubMedCentral

27.

Jaffrey SR, Snyder SH (2001) The biotin switch method for the detection of S-nitrosylated proteins. Sci STKE 2001:pl1. doi:10.1126/stke.2001.86.pl1

28.

Jung DW, Apel LM, Brierley GP (1992) Transmembrane gradients of free Na+ in isolated heart mitochondria estimated using a fluorescent probe. Am J Physiol 262:C1047–1055PubMed

29.

Kanaporis G, Brink PR, Valiunas V (2011) Gap junction permeability: selectivity for anionic and cationic probes. Am J Physiol Cell Physiol 300:C600–609. doi:10.1152/ajpcell.00316.2010 PubMedCrossRefPubMedCentral

30.

Kim B, Matsuoka S (2008) Cytoplasmic Na+-dependent modulation of mitochondrial Ca2+ via electrogenic mitochondrial Na+-Ca2+ exchange. J Physiol 586:1683–1697. doi:10.1113/jphysiol.2007.148726 PubMedCrossRefPubMedCentral

31.

Kohr MJ, Sun J, Aponte A, Wang G, Gucek M, Murphy E, Steenbergen C (2011) Simultaneous measurement of protein oxidation and S-nitrosylation during preconditioning and ischemia/reperfusion injury with resin-assisted capture. Circ Res 108:418–426. doi:10.1161/CIRCRESAHA.110.232173 PubMedCrossRefPubMedCentral

32.

Lau AF, Hatch-Pigott V, Crow DS (1991) Evidence that heart connexin43 is a phosphoprotein. J Mol Cell Cardiol 23:659–663PubMedCrossRef

33.

Li L, Lorenzo PS, Bogi K, Blumberg PM, Yuspa SH (1999) Protein kinase Cdelta targets mitochondria, alters mitochondrial membrane potential, and induces apoptosis in normal and neoplastic keratinocytes when overexpressed by an adenoviral vector. Mol Cell Biol 19:8547–8558PubMedPubMedCentral

34.

Li X, Heinzel FR, Boengler K, Schulz R, Heusch G (2004) Role of connexin 43 in ischemic preconditioning does not involve intercellular communication through gap junctions. J Mol Cell Cardiol 36:161–163PubMedCrossRef

35.

Lin J, Steenbergen C, Murphy E, Sun J (2009) Estrogen receptor-beta activation results in S-nitrosylation of proteins involved in cardioprotection. Circulation 120:245–254. doi:10.1161/CIRCULATIONAHA.109.868729 PubMedCrossRefPubMedCentral

36.

Miro-Casas E, Ruiz-Meana M, Agullo E, Stahlhofen S, Rodriguez-Sinovas A, Cabestrero A, Jorge I, Torre I, Vazquez J, Boengler K, Schulz R, Heusch G, Garcia-Dorado D (2009) Connexin43 in cardiomyocyte mitochondria contributes to mitochondrial potassium uptake. Cardiovasc Res 83:747–756. doi:10.1093/cvr/cvp157 PubMedCrossRef

37.

Mitchell P, Moyle J (1979) Respiratory-chain protonmotive stoichiometry. Biochem Soc Trans 7:887–894PubMed

38.

Murphy E, Steenbergen C (2005) Inhibition of GSK-3beta as a target for cardioprotection: the importance of timing, location, duration and degree of inhibition. Expert Opin Ther Targets 9:447–456. doi:10.1517/14728222.9.3.447 PubMedCrossRef

39.

Pain T, Yang XM, Critz SD, Yue Y, Nakano A, Liu GS, Heusch G, Cohen MV, Downey JM (2000) Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ Res 87:460–466PubMedCrossRef

40.

Park JW (1988) Reaction of S-nitrosoglutathione with sulfhydryl groups in protein. Biochem Biophys Res Commun 152:916–920PubMedCrossRef

41.

Ping P, Zhang J, Pierce WM Jr, Bolli R (2001) Functional proteomic analysis of protein kinase C epsilon signaling complexes in the normal heart and during cardioprotection. Circ Res 88:59–62PubMedCrossRef

42.

Plotkin LI, Manolagas SC, Bellido T (2002) Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem 277:8648–8657. doi:10.1074/jbc.M108625200 PubMedCrossRef

43.

Plum A, Hallas G, Magin T, Dombrowski F, Hagendorff A, Schumacher B, Wolpert C, Kim J, Lamers WH, Evert M, Meda P, Traub O, Willecke K (2000) Unique and shared functions of different connexins in mice. Curr Biol 10:1083–1091PubMedCrossRef

44.

Qian J, Zhang Q, Church JE, Stepp DW, Rudic RD, Fulton DJ (2010) Role of local production of endothelium-derived nitric oxide on cGMP signaling and S-nitrosylation. Am J Physiol Heart Circ Physiol 298:H112–118. doi:10.1152/ajpheart.00614.2009 PubMedCrossRefPubMedCentral

45.

Quist AP, Rhee SK, Lin H, Lal R (2000) Physiological role of gap-junctional hemichannels. Extracellular calcium-dependent isosmotic volume regulation. J Cell Biol 148:1063–1074PubMedCrossRefPubMedCentral

46.

Rassaf T, Totzeck M, Hendgen-Cotta UB, Shiva S, Heusch G, Kelm M (2014) Circulating nitrite contributes to cardioprotection by remote ischemic preconditioning. Circ Res 114:1601–1610. doi:10.1161/CIRCRESAHA.114.303822 PubMedCrossRef

47.

Ravichandran V, Seres T, Moriguchi T, Thomas JA, Johnston RB Jr (1994) S-thiolation of glyceraldehyde-3-phosphate dehydrogenase induced by the phagocytosis-associated respiratory burst in blood monocytes. J Biol Chem 269:25010–25015PubMed

48.

Redel A, Stumpner J, Smul TM, Lange M, Jazbutyte V, Ridyard DG, Roewer N, Kehl F (2013) Endothelial nitric oxide synthase mediates the first and inducible nitric oxide synthase mediates the second window of desflurane-induced preconditioning. J Cardiothorac Vasc Anesth 27:494–501. doi:10.1053/j.jvca.2012.04.015 PubMedCrossRef

49.

Retamal MA, Cortes CJ, Reuss L, Bennett MV, Saez JC (2006) S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes: induction by oxidant stress and reversal by reducing agents. Proc Natl Acad Sci USA 103:4475–4480. doi:10.1073/pnas.0511118103 PubMedCrossRefPubMedCentral

50.

Retamal MA, Schalper KA, Shoji KF, Bennett MV, Saez JC (2007) Opening of connexin 43 hemichannels is increased by lowering intracellular redox potential. Proc Natl Acad Sci USA 104:8322–8327. doi:10.1073/pnas.0702456104 PubMedCrossRefPubMedCentral

51.

Ripps H, Qian H, Zakevicius J (2002) Pharmacological enhancement of hemi-gap-junctional currents in Xenopus oocytes. J Neurosci Methods 121:81–92PubMedCrossRef

52.

Ripps H, Qian H, Zakevicius J (2004) Properties of connexin 26 hemichannels expressed in Xenopus oocytes. Cell Mol Neurobiol 24:647–665PubMedCrossRef

53.

Rodriguez-Sinovas A, Boengler K, Cabestrero A, Gres P, Morente M, Ruiz-Meana M, Konietzka I, Miro E, Totzeck A, Heusch G, Schulz R, Garcia-Dorado D (2006) Translocation of connexin 43 to the inner mitochondrial membrane of cardiomyocytes through the heat shock protein 90-dependent TOM pathway and its importance for cardioprotection. Circ Res 99:93–101. doi:10.1161/01.RES.0000230315.56904.de PubMedCrossRef

54.

Rodriguez-Sinovas A, Cabestrero A, Lopez D, Torre I, Morente M, Abellan A, Miro E, Ruiz-Meana M, Garcia-Dorado D (2007) The modulatory effects of connexin 43 on cell death/survival beyond cell coupling. Prog Biophys Mol Biol 94:219–232. doi:10.1016/j.pbiomolbio.2007.03.003 PubMedCrossRef

55.

Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC (2003) Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev 83:1359–1400. doi:10.1152/physrev.00007.2003 PubMed

56.

Saez JC, Retamal MA, Basilio D, Bukauskas FF, Bennett MV (2005) Connexin-based gap junction hemichannels: gating mechanisms. Biochim Biophys Acta 1711:215–224. doi:10.1016/j.bbamem.2005.01.014 PubMedCrossRefPubMedCentral

57.

Sanchez JA, Rodriguez-Sinovas A, Barba I, Miro-Casas E, Fernandez-Sanz C, Ruiz-Meana M, Alburquerque-Bejar JJ, Garcia-Dorado D (2013) Activation of RISK and SAFE pathways is not involved in the effects of Cx43 deficiency on tolerance to ischemia-reperfusion injury and preconditioning protection. Basic Res Cardiol 108:351. doi:10.1007/s00395-013-0351-3 PubMedCrossRef

58.

Sayed N, Baskaran P, Ma X, van den Akker F, Beuve A (2007) Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation. Proc Natl Acad Sci USA 104:12312–12317. doi:10.1073/pnas.0703944104 PubMedCrossRefPubMedCentral

59.

Schulman IH, Hare JM (2012) Regulation of cardiovascular cellular processes by S-nitrosylation. Biochim Biophys Acta 1820:752–762. doi:10.1016/j.bbagen.2011.04.002 PubMedCrossRef

60.

Schuppe-Koistinen I, Gerdes R, Moldeus P, Cotgreave IA (1994) Studies on the reversibility of protein S-thiolation in human endothelial cells. Arch Biochem Biophys 315:226–234PubMedCrossRef

61.

Schwanke U, Li X, Schulz R, Heusch G (2003) No ischemic preconditioning in heterozygous connexin 43-deficient mice—a further in vivo study. Basic Res Cardiol 98:181–182PubMed

62.

Serrano-Martin X, Payares G, Mendoza-Leon A (2006) Glibenclamide, a blocker of K+ (ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis. Antimicrob Agents Chemother 50:4214–4216. doi:10.1128/AAC.00617-06 PubMedCrossRefPubMedCentral

63.

Seth D, Stamler JS (2011) The SNO-proteome: causation and classifications. Curr Opin Chem Biol 15:129–136. doi:10.1016/j.cbpa.2010.10.012 PubMedCrossRefPubMedCentral

64.

Shiva S, Gladwin MT (2009) Shining a light on tissue NO stores: near infrared release of NO from nitrite and nitrosylated hemes. J Mol Cell Cardiol 46:1–3. doi:10.1016/j.yjmcc.2008.10.005 PubMedCrossRef

65.

Shiva S, Huang Z, Grubina R, Sun J, Ringwood LA, MacArthur PH, Xu X, Murphy E, Darley-Usmar VM, Gladwin MT (2007) Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res 100:654–661. doi:10.1161/01.RES.0000260171.52224.6b PubMedCrossRef

66.

Straub AC, Billaud M, Johnstone SR, Best AK, Yemen S, Dwyer ST, Looft-Wilson R, Lysiak JJ, Gaston B, Palmer L, Isakson BE (2011) Compartmentalized connexin 43 s-nitrosylation/denitrosylation regulates heterocellular communication in the vessel wall. Arterioscler Thromb Vasc Biol 31:399–407. doi:10.1161/ATVBAHA.110.215939 PubMedCrossRefPubMedCentral

67.

Sun J, Aponte AM, Kohr MJ, Tong G, Steenbergen C, Murphy E (2013) Essential role of nitric oxide in acute ischemic preconditioning: S-nitros(yl)ation versus sGC/cGMP/PKG signaling? Free Radic Biol Med 54:105–112. doi:10.1016/j.freeradbiomed.2012.09.005 PubMedCrossRefPubMedCentral

68.

Sun J, Kohr MJ, Nguyen T, Aponte AM, Connelly PS, Esfahani SG, Gucek M, Daniels MP, Steenbergen C, Murphy E (2012) Disruption of caveolae blocks ischemic preconditioning-mediated S-nitrosylation of mitochondrial proteins. Antioxid Redox Signal 16:45–56. doi:10.1089/ars.2010.3844 PubMedCrossRefPubMedCentral

69.

Sun J, Morgan M, Shen RF, Steenbergen C, Murphy E (2007) Preconditioning results in S-nitrosylation of proteins involved in regulation of mitochondrial energetics and calcium transport. Circ Res 101:1155–1163. doi:10.1161/CIRCRESAHA.107.155879 PubMedCrossRef

70.

Sun J, Murphy E (2010) Protein S-nitrosylation and cardioprotection. Circ Res 106:285–296. doi:10.1161/CIRCRESAHA.109.209452 PubMedCrossRefPubMedCentral

71.

Sun J, Picht E, Ginsburg KS, Bers DM, Steenbergen C, Murphy E (2006) Hypercontractile female hearts exhibit increased S-nitrosylation of the L-type Ca2+ channel alpha1 subunit and reduced ischemia/reperfusion injury. Circ Res 98:403–411. doi:10.1161/01.RES.0000202707.79018.0a PubMedCrossRef

72.

Symersky J, Osowski D, Walters DE, Mueller DM (2012) Oligomycin frames a common drug-binding site in the ATP synthase. Proc Natl Acad Sci USA 109:13961–13965. doi:10.1073/pnas.1207912109 PubMedCrossRefPubMedCentral

73.

Szabo I, Leanza L, Gulbins E, Zoratti M (2012) Physiology of potassium channels in the inner membrane of mitochondria. Pflugers Arch 463:231–246. doi:10.1007/s00424-011-1058-7 PubMedCrossRef

74.

Talukder MA, Yang F, Shimokawa H, Zweier JL (2010) eNOS is required for acute in vivo ischemic preconditioning of the heart: effects of ischemic duration and sex. Am J Physiol Heart Circ Physiol 299:H437–445. doi:10.1152/ajpheart.00384.2010 PubMedCrossRefPubMedCentral

75.

Ting HP, Wilson DF, Chance B (1970) Effects of uncouplers of oxidative phosphorylation on the specific conductance of bimolecular lipid membranes. Arch Biochem Biophys 141:141–146PubMedCrossRef

76.

Tsikas D (2008) A critical review and discussion of analytical methods in the l-arginine/nitric oxide area of basic and clinical research. Anal Biochem 379:139–163. doi:10.1016/j.ab.2008.04.018 PubMedCrossRef

77.

Turrens JF, Boveris A (1980) Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J 191:421–427PubMedPubMedCentral

78.

Wang H, Viatchenko-Karpinski S, Sun J, Gyorke I, Benkusky NA, Kohr MJ, Valdivia HH, Murphy E, Gyorke S, Ziolo MT (2010) Regulation of myocyte contraction via neuronal nitric oxide synthase: role of ryanodine receptor S-nitrosylation. J Physiol 588:2905–2917. doi:10.1113/jphysiol.2010.192617 PubMedCrossRefPubMedCentral

79.

Wang N, De Bock M, Antoons G, Gadicherla AK, Bol M, Decrock E, Evans WH, Sipido KR, Bukauskas FF, Leybaert L (2012) Connexin mimetic peptides inhibit Cx43 hemichannel opening triggered by voltage and intracellular Ca2+ elevation. Basic Res Cardiol 107:304. doi:10.1007/s00395-012-0304-2 PubMedCrossRefPubMedCentral

80.

Wilson DF, Chance B (1966) Reversal of azide inhibition by uncouplers. Biochem Biophys Res Commun 23:751–756PubMedCrossRef

81.

Zhang J, Jin B, Li L, Block ER, Patel JM (2005) Nitric oxide-induced persistent inhibition and nitrosylation of active site cysteine residues of mitochondrial cytochrome-c oxidase in lung endothelial cells. Am J Physiol Cell Physiol 288:C840–849. doi:10.1152/ajpcell.00325.2004 PubMedCrossRef

82.

Ziolo MT, Bers DM (2003) The real estate of NOS signaling: location, location, location. Circ Res 92:1279–1281. doi:10.1161/01.RES.0000080783.34092.AF PubMedCrossRef

Title: S-nitrosation of mitochondrial connexin 43 regulates mitochondrial function
Authors: Daniel Soetkamp
Tiffany T. Nguyen
Sara Menazza
Christine Hirschhäuser
Ulrike B. Hendgen-Cotta
Tienush Rassaf
Klaus D. Schlüter
Kerstin Boengler
Elizabeth Murphy
Rainer Schulz
Publication date: 01-09-2014
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 5/2014
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-014-0433-x

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