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Dr Emmanuel Dupont

Senior Lecturer

Qualifications: PhD

Email:

Further information

Publications

Highlights

  • Kreuzberg MM, Liebermann M, Segschneider S, Dobrowolski R, Dobrzynski H, Kaba R, Rowlinson G, Dupont E, Severs NJ, Willecke K. (2009) 'Human connexin31.9, unlike its orthologous protein connexin30.2 in the mouse, is not detectable in the human cardiac conduction system'. ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 46 (4), pp. 553-559.
    doi: 10.1016/j.yjmcc.2008.12.007
  • Bruce AF, Rothery S, Dupont E, Severs NJ. (2008) 'Gap junction remodelling in human heart failure is associated with increased interaction of connexin43 with ZO-1'. Elsevier Science BV CARDIOVASC RES, 77 (4), pp. 757-765.
    doi: 10.1093/cvr/cvm083
    Full text is available at: http://epubs.surrey.ac.uk/205758/

    Abstract

    Aims Remodelling of gap junctions, involving reduction of total gap junction quantity and down-regulation of connexin43 (Cx43), contributes to the arrhythmic substrate in congestive heart failure. However, little is known of the underlying mechanisms. Recent studies from in vitro systems suggest that the connexin-interacting protein zonula occludens-1 (ZO-1) is a potential mediator of gap junction remodelling. We therefore examined the hypothesis that ZO-1 contributes to reduced expression of Cx43 gap junctions in congestive heart failure. Methods and results Left ventricular myocardium from healthy control human hearts (n = 5) was compared with that of explanted hearts from transplant patients with end-stage congestive heart failure due to idiopathic dilated cardiomyopathy (DCM; n = 5) or ischaemic cardiomyopathy (ICM; n = 5). Immunoconfocal and immunoelectron microscopy showed that ZO-1 is specifically localized to the intercalated disc of cardiomyocytes in control and failing ventricles. ZO-1 protein levels were significantly increased in both DCM and ICM (P = 0.0025), showing a significant, negative correlation to Cx43 levels (P = 0.0029). There was, however, no significant alteration of ZO-1 mRNA (P = 0.537). Double immunolabelling demonstrated that a proportion of ZO-1 label is co-localized with Cx43, and that co-localization of Cx43 with ZO-1 is significantly increased in the failing ventricle (P = 0.003). Interaction between the two proteins was confirmed by co-immunoprecipitation. The proportion of Cx43 that co-immunoprecipitates with ZO-1 was significantly increased in the failing heart. Conclusion Our findings suggest that ZO-1, by interacting with Cx43, plays a role in the down-regulation and decreased size of Cx43 gap junctions in congestive heart failure.

  • Grikscheit K, Thomas N, Bruce AF, Rothery S, Chan J, Severs NJ, Dupont E. (2008) 'Coexpression of connexin45 with connexin43 decreases gap junction size'. INFORMA HEALTHCARE CELL COMMUNICATION AND ADHESION, 15 (1-2), pp. 185-193.
    doi: 10.1080/15419060802013943
  • Matsushita T, Rama A, Charolidi N, Dupont E, Severs NJ. (2007) 'Relationship of connexin43 expression to phenotypic modulation in cultured human aortic smooth muscle cells'. ELSEVIER GMBH, URBAN & FISCHER VERLAG EUR J CELL BIOL, 86 (10), pp. 617-628.
    doi: 10.1016/j.ejcb.2007.06.005
  • Kanagaratnam P, Dupont E, Rothery S, Coppen S, Severs NJ, Peters NS. (2006) 'Human atrial conduction and arrhythmogenesis correlates with conformational exposure of specific epitopes on the connexin40 carboxyl tail'. ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 40 (5), pp. 675-687.
    doi: 10.1016/j.yjmcc.2006.01.002
  • Uzumcu A, Norgett EE, Dindar A, Uyguner O, Nisli K, Kayserili H, Sahin SE, Dupont E, Severs NJ, Leigh IM, Yuksel-Apak M, Kelsell DP, Wollnik B. (2006) 'Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome'. B M J PUBLISHING GROUP J MED GENET, 43 (2) Article number e5
    doi: 10.1136/jmg.2005.032904

Journal articles

  • Desplantez T, Halliday D, Dupont E, Severs NJ, Weingart R. (2011) 'Influence of V5/6-His Tag on the Properties of Gap Junction Channels Composed of Connexin43, Connexin40 or Connexin45'. SPRINGER JOURNAL OF MEMBRANE BIOLOGY, 240 (3), pp. 139-150.
    doi: 10.1007/s00232-011-9352-z
    Full text is available at: http://epubs.surrey.ac.uk/205752/
  • Ng FS, Owusu-Agyei AA, Chang ET, Chowdhury RA, Patel PM, Larsen BD, Haugan K, Dupont E, Lyon AR, Peters NS. (2010) 'ZP1210, a Novel Gap Junction Modulator, Attenuates Conduction Slowing and Prevents Cx43 Dephosphorylation During Metabolic Stress'. CIRCULATION, 122 (21)
  • Kreuzberg MM, Liebermann M, Segschneider S, Dobrowolski R, Dobrzynski H, Kaba R, Rowlinson G, Dupont E, Severs NJ, Willecke K. (2009) 'Human connexin31.9, unlike its orthologous protein connexin30.2 in the mouse, is not detectable in the human cardiac conduction system'. ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 46 (4), pp. 553-559.
    doi: 10.1016/j.yjmcc.2008.12.007
  • Severs NJ, Bruce AF, Dupont E, Rothery S. (2008) 'Remodelling of gap junctions and connexin expression in diseased myocardium'. OXFORD UNIV PRESS CARDIOVASCULAR RESEARCH, 80 (1), pp. 9-19.
    doi: 10.1093/cvr/cvn133
    Full text is available at: http://epubs.surrey.ac.uk/205756/
  • Bruce AF, Rothery S, Dupont E, Severs NJ. (2008) 'Gap junction remodelling in human heart failure is associated with increased interaction of connexin43 with ZO-1'. Elsevier Science BV CARDIOVASC RES, 77 (4), pp. 757-765.
    doi: 10.1093/cvr/cvm083
    Full text is available at: http://epubs.surrey.ac.uk/205758/

    Abstract

    Aims Remodelling of gap junctions, involving reduction of total gap junction quantity and down-regulation of connexin43 (Cx43), contributes to the arrhythmic substrate in congestive heart failure. However, little is known of the underlying mechanisms. Recent studies from in vitro systems suggest that the connexin-interacting protein zonula occludens-1 (ZO-1) is a potential mediator of gap junction remodelling. We therefore examined the hypothesis that ZO-1 contributes to reduced expression of Cx43 gap junctions in congestive heart failure. Methods and results Left ventricular myocardium from healthy control human hearts (n = 5) was compared with that of explanted hearts from transplant patients with end-stage congestive heart failure due to idiopathic dilated cardiomyopathy (DCM; n = 5) or ischaemic cardiomyopathy (ICM; n = 5). Immunoconfocal and immunoelectron microscopy showed that ZO-1 is specifically localized to the intercalated disc of cardiomyocytes in control and failing ventricles. ZO-1 protein levels were significantly increased in both DCM and ICM (P = 0.0025), showing a significant, negative correlation to Cx43 levels (P = 0.0029). There was, however, no significant alteration of ZO-1 mRNA (P = 0.537). Double immunolabelling demonstrated that a proportion of ZO-1 label is co-localized with Cx43, and that co-localization of Cx43 with ZO-1 is significantly increased in the failing ventricle (P = 0.003). Interaction between the two proteins was confirmed by co-immunoprecipitation. The proportion of Cx43 that co-immunoprecipitates with ZO-1 was significantly increased in the failing heart. Conclusion Our findings suggest that ZO-1, by interacting with Cx43, plays a role in the down-regulation and decreased size of Cx43 gap junctions in congestive heart failure.

  • Grikscheit K, Thomas N, Bruce AF, Rothery S, Chan J, Severs NJ, Dupont E. (2008) 'Coexpression of connexin45 with connexin43 decreases gap junction size'. INFORMA HEALTHCARE CELL COMMUNICATION AND ADHESION, 15 (1-2), pp. 185-193.
    doi: 10.1080/15419060802013943
  • Matsushita T, Rama A, Charolidi N, Dupont E, Severs NJ. (2007) 'Relationship of connexin43 expression to phenotypic modulation in cultured human aortic smooth muscle cells'. ELSEVIER GMBH, URBAN & FISCHER VERLAG EUR J CELL BIOL, 86 (10), pp. 617-628.
    doi: 10.1016/j.ejcb.2007.06.005
  • Desplantez T, Dupont E, Severs NJ, Weingart R. (2007) 'Gap junction channels and cardiac impulse propagation'. SPRINGER JOURNAL OF MEMBRANE BIOLOGY, 218 (1-3), pp. 13-28.
    doi: 10.1007/s00232-007-9046-8
  • Kanagaratnam P, Dupont E, Rothery S, Coppen S, Severs NJ, Peters NS. (2006) 'Human atrial conduction and arrhythmogenesis correlates with conformational exposure of specific epitopes on the connexin40 carboxyl tail'. ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 40 (5), pp. 675-687.
    doi: 10.1016/j.yjmcc.2006.01.002
  • Rama A, Matsushita T, Charolidi N, Rothery S, Dupont E, Severs NJ. (2006) 'Up-regulation of connexin43 correlates with increased synthetic activity and enhanced contractile differentiation in TGF-beta-treated human aortic smooth muscle cells'. ELSEVIER GMBH, URBAN & FISCHER VERLAG EUR J CELL BIOL, 85 (5), pp. 375-386.
    doi: 10.1016/j.ejcb.2005.11.007
  • Uzumcu A, Norgett EE, Dindar A, Uyguner O, Nisli K, Kayserili H, Sahin SE, Dupont E, Severs NJ, Leigh IM, Yuksel-Apak M, Kelsell DP, Wollnik B. (2006) 'Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome'. B M J PUBLISHING GROUP J MED GENET, 43 (2) Article number e5
    doi: 10.1136/jmg.2005.032904
  • Severs NJ, Dupont E, Thomas N, Kaba R, Rothery S, Jain R, Sharpey K, Fry CH. (2006) 'Alterations in cardiac connexin expression in cardiomyopathies'. KARGER CARDIOVASCULAR GAP JUNCTIONS, 42, pp. 228-242.
    doi: 10.1159/000092572
  • Severs NJ, Dupont E, Thomas N, Kaba R, Rothery S, Jain R, Sharpey K, Fry CH. (2006) 'Alterations in cardiac connexin expression in cardiomyopathies.'. Adv Cardiol, Switzerland: 42, pp. 228-242.
    doi: 10.1159/000092572
  • Tribulova N, Dupont E, Soukup T, Okruhlicova L, Severs NJ. (2005) 'Sex differences in connexin-43 expression in left ventricles of aging rats'. ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY PHYSIOL RES, 54 (6), pp. 705-708.
    Full text is available at: http://epubs.surrey.ac.uk/205769/

    Abstract

    Cardiac gap junctions have been implicated in maintaining intercellular electrical and metabolic couplings. The abnormalities in connexin-43 (Cx43) lead to conduction defects and contractile dysfunction. We have evaluatedthe expression and phoshorylation status of Cx43 in the left ventricular myocardium of male and female 16-month-old rats submitted to 14-week L-thyroxine (T4) treatment. Western blot analysis revealed the presence of fully or intermediately phosphorylated and unphosphorylated forms of Cx43. We have found no significant differences in Cx43 expression and phosphorylation between T4-treated and control untreated animals. However, expression of Cx43 was significantly higher in female compared to male rats. We conclude that T4 administration has no effect on Cx43 expression, but there are sex-dependent differences in Cx43 expression in the left ventricles between aging male and female rats.

Conference papers

  • Ng FS, Lyon AR, Shadi IT, Chang ETY, Chowdhury RA, Dupont E, Peters NS. (2010) 'GAP JUNCTIONAL UNCOUPLING WITH CARBENOXOLONE SLOWS CONDUCTION AND INCREASES VULNERABILITY TO VENTRICULAR ARRHYTHMIAS IN STRUCTURALLY NORMAL HEARTS: AN OPTICAL MAPPING STUDY'. B M J PUBLISHING GROUP HEART, Manchester, ENGLAND: Annual Conference and Exhibition of the British-Cardiovascular-Society 96, pp. A5-A6.
    doi: 10.1136/hrt.2010.195941.3
  • Ng FS, Lyon AR, Shadi IT, Chang ETY, Chowdhury RA, Dupont E, Peters NS. (2010) 'MODULATION OF GAP JUNCTIONAL COUPLING AS AN ANTI-ARRHYTHMIC STRATEGY TO PREVENT REPERFUSION VENTRICULAR ARRHYTHMIAS'. B M J PUBLISHING GROUP HEART, Manchester, ENGLAND: Annual Conference and Exhibition of the British-Cardiovascular-Society 96, pp. A2-A3.
    doi: 10.1136/hrt.2010.196113.17
  • Rowlinson G, Dupont E, Daubeney P, Severs NJ. (2008) 'Connexin40 is expressed in the right ventricles of patients with congenital heart malformations'. ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Athens, GREECE: 28th Annual Meeting of the European Section of the International-Society-for-Heart-Research 44 (4), pp. 733-733.
    doi: 10.1016/j.yjmcc.2008.02.053
  • Grikscheit K, Bruce AF, Dupont E, Thomas N, Severs NJ. (2008) 'Increased expression of connexin45, as found in human heart failure, decreases gap junction size'. ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Athens, GREECE: 28th Annual Meeting of the European Section of the International-Society-for-Heart-Research 44 (4), pp. 732-733.
    doi: 10.1016/j.yjmcc.2008.02.052
  • Chowdhury RA, Kaba RA, Patel PM, Patel HN, Dupont E, Severs NJ, Wit AL, Peters NS. (2006) 'Changes in connexin43 immunolabelling are not associated with changes in connexin45 or connexin40 labelling in the canine infarct border zone'. OXFORD UNIV PRESS EUROPEAN HEART JOURNAL, Barcelona, SPAIN: World Congress of Cardiology 27, pp. 720-721.
  • Charolidi N, Dupont E, Rama A, Matsushita T, Severs NJ. (2006) 'Gap-junctional communication and the control of vascular smooth muscle cell phenotype'. ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Toronto, CANADA: 28th Annual International-Society-for-Heart-Research North American Section Meeting 40 (6), pp. 1012-1012.
    doi: 10.1016/j.yjmcc.2006.03.267
  • Bruce AF, Rothery S, Dupont E, Severs NJ. (2006) 'Does zonula occludens 1 play a role in remodelling of connexin43 gap junctions in the failing human ventricle?'. ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Toronto, CANADA: 28th Annual International-Society-for-Heart-Research North American Section Meeting 40 (6), pp. 948-949.
    doi: 10.1016/j.yjmcc.2006.03.093
  • Thomas N, Dupont E, Halliday D, Fry CH, Severs NJ. (2006) 'An inducible cell system to investigate connexin co-expression and action potential propagation within the heart'. ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Toronto, CANADA: 28th Annual International-Society-for-Heart-Research North American Section Meeting 40 (6), pp. 984-984.
    doi: 10.1016/j.yjmcc.2006.03.190