Administration of FGF-2 to the heart stimulates connexin-43 phosphorylation at protein kinase C target sites.
Fibroblast growth factor-2 (FGF-2) confers acute, preconditioning-like cardiac resistance to ischemic injury in a protein kinase C (PKC)-dependent fashion. One of the downstream targets of PKC is the gap junction protein connexin-43 (Cx43). We thus examined the effects of FGF-2 on Cx43 phosphorylation at specific PKC sites in the adult heart. Rat hearts perfused ex vivo for 20 min with an FGF-2-containing solution displayed increased levels of phosphorylated 44-45 kDa Cx43, assessed by western blotting. In addition, FGF-2 significantly upregulated phosphorylation of the PKC target serines 262 and 368 on Cx43 at intercalated disks, assessed using phosphospecific antibodies in immunolocalization and western blotting assays. Our data show that FGF-2, administered by perfusion, can alter the phosphorylation status of Cx43 at cardiomyocyte intercalated disks, and suggest a link between phosphorylation of Cx43 at specific PKC sites and FGF-2 cardioprotection.
Srisakuldee
Wattamon
W
Department of Human Anatomy and Cell Sciences, Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
Nickel
Barbara E
BE
Fandrich
Robert R
RR
Jiang
Zhi-Sheng
ZS
Kardami
Elissavet
E
D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D017629:Gap Junctions / Q000378:metabolism; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism
D018031:Connexin 43; D016222:Fibroblast Growth Factor 2; D012694:Serine; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon