Document Detail

No impact of protein phosphatases on connexin 43 phosphorylation in ischemic preconditioning.
MedLine Citation:
PMID:  18835920     Owner:  NLM     Status:  MEDLINE    
Cardiac connexin 43 (Cx43) is involved in infarct propagation, and the uncoupling of Cx43-formed channels reduces infarct size. Cx43-formed channels open upon Cx43 dephosphorylation, and ischemic preconditioning (IP) prevents the ischemia-induced Cx43 dephosphorylation. In addition to the sarcolemma, Cx43 is also present in the cardiomyocyte mitochondria. We now examined the interaction of Cx43 with protein phosphatases PP1alpha, PP2Aalpha, and PP2Balpha and the role of such interaction for Cx43 phosphorylation in preconditioned myocardium. Infarct size (in %area at risk) in left ventricular anterior myocardium of Göttinger minipigs subjected to 90 min of low-flow ischemia and 120 min of reperfusion was 23.1 +/- 2.7 [n = 7, nonpreconditioned (NIP) group] and was reduced by IP to 10.0 +/- 3.2 (n = 6, P < 0.05). Mitochondrial and gap junctional Cx43 dephosphorylation increased after 85 min of ischemia in NIP myocardium, whereas Cx43 phosphorylation was preserved with IP. PP2Aalpha and PP1alpha, but not PP2Balpha, were detected by Western blot analysis in the left ventricular myocardium. Cx43 coprecipitated with PP2Aalpha but not with PP1alpha. Although the total PP2Aalpha immunoreactivity (confocal laser scan) was increased to 154 +/- 24% and 194 +/- 13% of baseline (P < 0.05) after 85 min of ischemia in NIP and IP myocardium, respectively, the PP2A activities were similar between the groups. The amount of PP2Aalpha coimmunoprecipitated with Cx43 remained unchanged. Only PP2Aalpha coprecipitates with Cx43 in pig myocardium. This interaction is not affected by IP, suggesting that PP2Aalpha is not involved in the prevention of the ischemia-induced Cx43 dephosphorylation by IP.
Andreas Totzeck; Kerstin Boengler; Anita van de Sand; Ina Konietzka; Petra Gres; David Garcia-Dorado; Gerd Heusch; Rainer Schulz
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-03
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  295     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-10     Completed Date:  2008-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2106-12     Citation Subset:  IM    
Institut für Pathophysiologie, Universitätsklinikum Essen, Hufelandstrabe 55, 45122, Essen, Germany.
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MeSH Terms
Calcineurin / metabolism
Connexin 43 / metabolism*
Disease Models, Animal
Gap Junctions / enzymology
Ischemic Preconditioning, Myocardial*
Mitochondria, Heart / enzymology
Myocardial Infarction / enzymology,  pathology,  prevention & control*
Myocardial Reperfusion Injury / enzymology,  pathology,  prevention & control*
Myocardium / enzymology*,  pathology
Protein Binding
Protein Phosphatase 1 / metabolism
Protein Phosphatase 2 / metabolism*
Swine, Miniature
Reg. No./Substance:
0/Connexin 43; EC; EC protein, rat; EC Phosphatase 1; EC Phosphatase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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