Copyright © 2005, European Society of Cardiology
Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning
aInstitut für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstr. 55, 45122 Essen, Germany
bDipartimento di Chimica Biologica, Universita di Padova, Italy
cServicio de Cardiologia, Hospital Vall d'Hebron, Barcelona, Spain
* Corresponding author. Email address: rainer_schulz{at}uni-essen.de
Objective: Connexin 43 (Cx43) is involved in infarct size reduction by ischemic preconditioning (IP); the underlying mechanism of protection, however, is unknown. Since mitochondria have been proposed to be involved in IP's protection, the present study analyzed whether Cx43 is localized at mitochondria of cardiomyocytes and whether such localization is affected by IP.
Methods and results: Western blot analysis on mitochondrial preparations isolated from rat, mouse, pig, and human hearts showed the presence of Cx43. The preparations were not contaminated with markers for other cell compartments. The localization of Cx43 to mitochondria was also confirmed by FACS sorting (double staining with MitoTracker Red and Cx43) and immuno-electron and confocal microscopy. To study the role of Cx43 in IP, mitochondria were isolated from the ischemic anterior wall (AW) and the control posterior wall (PW) of pig myocardium at the end of 90 min low-flow ischemia without (n = 13) or with (n = 13) a preceding preconditioning cycle of 10 min ischemia and 15 min reperfusion. With IP, the mitochondrial Cx43/adenine nucleotide transporter ratio was 3.4 ± 0.7 fold greater in AW than in PW, whereas the ratio remained unchanged in non-preconditioned myocardium (1.1 ± 0.2, p<0.05). The enhancement of the mitochondrial Cx43 protein level occurred rapidly, since an increase of mitochondrial Cx43 was already detected with two cycles of 5 min ischemia/reperfusion in isolated rat hearts to 262 ± 63% of baseline.
Conclusion: These data demonstrate that Cx43 is localized at cardiomyocyte mitochondria and that IP enhances such mitochondrial localization.
KEYWORDS Connexin; Mitochondria; Preconditioning
1 This author contributed equally to the manuscript.
2 K.B. was awarded the Servier Research Fellowship of the European Section of the International Society for Heart Research for this project.
* Stefan Dhein, University of Leipzig served as guest editor.
Time for primary review 40 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Boengler, R. Schulz, and G. Heusch Loss of cardioprotection with ageing Cardiovasc Res, July 15, 2009; 83(2): 247 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Miro-Casas, M. Ruiz-Meana, E. Agullo, S. Stahlhofen, A. Rodriguez-Sinovas, A. Cabestrero, I. Jorge, I. Torre, J. Vazquez, K. Boengler, et al. Connexin43 in cardiomyocyte mitochondria contributes to mitochondrial potassium uptake Cardiovasc Res, June 8, 2009; (2009) cvp157v2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Srisakuldee, M. M. Jeyaraman, B. E. Nickel, S. Tanguy, Z.-S. Jiang, and E. Kardami Phosphorylation of connexin-43 at serine 262 promotes a cardiac injury-resistant state Cardiovasc Res, June 5, 2009; (2009) cvp142v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lu, H. K. Haider, S. Jiang, and M. Ashraf Sca-1+ Stem Cell Survival and Engraftment in the Infarcted Heart: Dual Role for Preconditioning-Induced Connexin-43 Circulation, May 19, 2009; 119(19): 2587 - 2596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Naitoh, T. Yano, T. Miura, T. Itoh, T. Miki, M. Tanno, T. Sato, H. Hotta, Y. Terashima, and K. Shimamoto Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H396 - H403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch, K. Boengler, and R. Schulz Cardioprotection: Nitric Oxide, Protein Kinases, and Mitochondria Circulation, November 4, 2008; 118(19): 1915 - 1919. [Full Text] [PDF]
|
|
|
|
|
|
A. Totzeck, K. Boengler, A. van de Sand, I. Konietzka, P. Gres, D. Garcia-Dorado, G. Heusch, and R. Schulz No impact of protein phosphatases on connexin 43 phosphorylation in ischemic preconditioning Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H2106 - H2112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-H. Wang, C.-I Kung, Y.-Y. Tseng, Y.-C. Lin, C.-H. Chen, C.-H. Tsai, and H.-I Yeh Activation of endothelial cells to pathological status by down-regulation of connexin43 Cardiovasc Res, August 1, 2008; 79(3): 509 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Murphy and C. Steenbergen Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury Physiol Rev, April 1, 2008; 88(2): 581 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ytrehus Hypoxia-inducible factor 1{alpha}: a new piece in the preconditioning puzzle Cardiovasc Res, February 1, 2008; 77(3): 443 - 444. [Full Text] [PDF]
|
|
|
|
|
|
M. Ruiz-Meana, A. Rodriguez-Sinovas, A. Cabestrero, K. Boengler, G. Heusch, and D. Garcia-Dorado Mitochondrial connexin43 as a new player in the pathophysiology of myocardial ischaemia-reperfusion injury Cardiovasc Res, January 15, 2008; 77(2): 325 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-D. Jiao, V. Garg, B. Yang, and K. Hu Novel functional role of heat shock protein 90 in ATP-sensitive K+ channel-mediated hypoxic preconditioning Cardiovasc Res, January 1, 2008; 77(1): 126 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ferdinandy, R. Schulz, and G. F. Baxter Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning Pharmacol. Rev., December 1, 2007; 59(4): 418 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Murphy and C. Steenbergen Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury Cardiovasc Res, August 1, 2007; 75(3): 478 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Garg and K. Hu Protein kinase C isoform-dependent modulation of ATP-sensitive K+ channels in mitochondrial inner membrane Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H322 - H332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Lascano and J. A. Negroni Gap junctions in preconditioning against arrhythmias Cardiovasc Res, June 1, 2007; 74(3): 341 - 342. [Full Text] [PDF]
|
|
|
|
|
|
K. Boengler, I. Konietzka, A. Buechert, Y. Heinen, D. Garcia-Dorado, G. Heusch, and R. Schulz Loss of ischemic preconditioning's cardioprotection in aged mouse hearts is associated with reduced gap junctional and mitochondrial levels of connexin 43 Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1764 - H1769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Martin, R. Schulz, H. Post, K. Boengler, M. Kelm, P. Kleinbongard, P. Gres, A. Skyschally, I. Konietzka, and G. Heusch Microdialysis-based analysis of interstitial NO in situ: NO synthase-independent NO formation during myocardial ischemia Cardiovasc Res, April 1, 2007; 74(1): 46 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Boengler, R Schulz, and G Heusch Connexin 43 signalling and cardioprotection Heart, December 1, 2006; 92(12): 1724 - 1727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. B. Francis and C. W. Lo Primordial germ cell deficiency in the connexin 43 knockout mouse arises from apoptosis associated with abnormal p53 activation Development, September 1, 2006; 133(17): 3451 - 3460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Halestrap Mitochondria and Preconditioning: A Connexin Connection? Circ. Res., July 7, 2006; 99(1): 10 - 12. [Full Text] [PDF]
|
|
|
|
|
|
A. Rodriguez-Sinovas, K. Boengler, A. Cabestrero, P. Gres, M. Morente, M. Ruiz-Meana, I. Konietzka, E. Miro, A. Totzeck, G. Heusch, et al. 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., July 7, 2006; 99(1): 93 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Garcia-Dorado, J. Vinten-Johansen, and H. M. Piper Bringing preconditioning and postconditioning into focus Cardiovasc Res, May 1, 2006; 70(2): 167 - 169. [Full Text] [PDF]
|
|
|
|
|
|
D. Garcia-Dorado, A. Rodriguez-Sinovas, M. Ruiz-Meana, J. Inserte, L. Agullo, and A. Cabestrero The end-effectors of preconditioning protection against myocardial cell death secondary to ischemia-reperfusion Cardiovasc Res, May 1, 2006; 70(2): 274 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Naitoh, Y. Ichikawa, T. Miura, Y. Nakamura, T. Miki, Y. Ikeda, H. Kobayashi, M. Nishihara, K. Ohori, and K. Shimamoto MitoKATP channel activation suppresses gap junction permeability in the ischemic myocardium by an ERK-dependent mechanism Cardiovasc Res, May 1, 2006; 70(2): 374 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Piper and E. A. Martinson Cardiovascular Research speeds up-Even more Cardiovasc Res, March 1, 2006; 69(4): 773 - 776. [Full Text] [PDF]
|
|
|
|
|
|
F. R. Heinzel, Y. Luo, X. Li, K. Boengler, A. Buechert, D. Garcia-Dorado, F. Di Lisa, R. Schulz, and G. Heusch Impairment of Diazoxide-Induced Formation of Reactive Oxygen Species and Loss of Cardioprotection in Connexin 43 Deficient Mice Circ. Res., September 16, 2005; 97(6): 583 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dhein New, emerging roles for cardiac connexins. Mitochondrial Cx43 raises new questions Cardiovasc Res, August 1, 2005; 67(2): 179 - 181. [Full Text] [PDF]
|
|