Journal
PHARMACOLOGY & THERAPEUTICS
Volume 153, Issue -, Pages 90-106Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2015.06.005
Keywords
Connexin 43; Heart; Brain; Mitochondria; Neuroprotection; Cardioprotection
Categories
Funding
- National Research Fund of Hungary [ANN 107803, K 109737]
- US National Institutes of Health [GM55632]
- Fund for Scientific Research Flanders, Belgium [G.0298.11, G.0571.12, G.0A54.13, G.0320.15N]
- Inter-university Attraction Poles Program (Belgian Science Policy) [P7/10]
- Hungarian Scientific Research Fund [OTKA PD 106001]
- National Excellence Program of Hungary [TAMOP 4.2.4.A/2-11-1-2012-0001]
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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. (C) 2015 Elsevier Inc. All rights reserved.
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