title: Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection.
abstract: Connexins are widely distributed proteins in the body that are crucially important for heart and brain functions. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localization at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in the mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodeling or heart failure, and post-translationally connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the connexins, namely connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injuries as well as protection from it. Therefore, the current review will focus on the importance of connexin 43 for irreversible injury of heart and brain tissues following ischemia/reperfusion and will highlight the importance of connexin 43 as an emerging therapeutic target in cardio- and neuroprotection.
authors.affiliation: Institut für Physiologie, JustusLiebig Universität Giessen, Gießen, Germany. Electronic address: rainer.schulz@physiologie.med.uni-giessen.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.affiliation: Institut für Physiologie, JustusLiebig Universität Giessen, Gießen, Germany.
authors.forename: Philipp Maximilian
authors.initials: PM
authors.lastname: Görge
authors.affiliation: Cardiovascular Research Group, Department of Biochemistry, Faculty of Medicine, University of Szeged, Hungary; Pharmahungary Group, Szeged, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Görbe
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; Pharmahungary Group, Szeged, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lampe
authors.affiliation: Physiology Group, Department Basic Medical Sciences, Ghent University, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Leybaert
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018031:Connexin 43 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006321:Heart / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism*; D000066829:Neuroprotection / Q000187:drug effects*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy
chemical_list: D002316:Cardiotonic Agents; D018031:Connexin 43
keywords: Brain; Cardioprotection; Connexin 43; Heart; Mitochondria; Neuroprotection