Administration of FGF-2 to the heart stimulates connexin-43 phosphorylation at protein kinase C target sites

被引:24
作者
Srisakuldee, W
Nickel, BE
Fandrich, RR
Jiang, ZS
Kardami, E
机构
[1] Univ Manitoba, Inst Cardiovasc Sci, St Boniface Res Ctr, Dept Human Anat & Cell Sci, Winnipeg, MB R2H 2A6, Canada
[2] Univ Manitoba, Inst Cardiovasc Sci, St Boniface Res Ctr, Dept Physiol, Winnipeg, MB R2H 2A6, Canada
基金
加拿大健康研究院;
关键词
fibroblast growth factor-2; cardioprotection; connexin-43; phosphorylation; protein kinase C;
D O I
10.1080/15419060600631326
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:13 / 19
页数:7
相关论文
共 24 条
[1]   Protein kinase C-α and -ε modulate connexin-43 phosphorylation in human heart [J].
Bowling, N ;
Huang, XD ;
Sandusky, GE ;
Fouts, RL ;
Mintze, K ;
Esterman, M ;
Allen, PD ;
Maddi, R ;
McCall, E ;
Vlahos, CJ .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2001, 33 (04) :789-798
[2]   Biological activities of fibroblast growth factor-2 in the adult myocardium [J].
Detillieux, KA ;
Sheikh, F ;
Kardami, E ;
Cattini, PA .
CARDIOVASCULAR RESEARCH, 2003, 57 (01) :8-19
[3]   Phosphorylation of serine 262 in the gap junction protein connexin-43 regulates DNA synthesis in cell-cell contact forming cardiomyocytes [J].
Doble, BW ;
Dang, XT ;
Ping, PP ;
Fandrich, RR ;
Nickel, BE ;
Jin, Y ;
Cattini, PA ;
Kardami, E .
JOURNAL OF CELL SCIENCE, 2004, 117 (03) :507-514
[4]   Fibroblast growth factor-2 decreases metabolic coupling and stimulates phosphorylation as well as masking of connexin43 epitopes in cardiac myocytes [J].
Doble, BW ;
Chen, YJ ;
Bose, DG ;
Litchfield, DW ;
Kardami, E .
CIRCULATION RESEARCH, 1996, 79 (04) :647-658
[5]   The ε subtype of protein kinase C is required for cardiomyocyte connexin-43 phosphorylation [J].
Doble, BW ;
Ping, PP ;
Kardami, E .
CIRCULATION RESEARCH, 2000, 86 (03) :293-301
[6]   Gap junction-mediated spread of cell injury and death during myocardial ischemia-reperfusion [J].
García-Dorado, D ;
Rodríguez-Sinovas, A ;
Ruiz-Meana, M .
CARDIOVASCULAR RESEARCH, 2004, 61 (03) :386-401
[7]   PKC-ε is upstream and PKC-α is downstream of mitoKATP channels in the signal transduction pathway of ischemic preconditioning of human myocardium [J].
Hassouna, A ;
Matata, BM ;
Galiñanes, M .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2004, 287 (05) :C1418-C1425
[8]   Cardioprotection by ε-protein kinase C activation from ischemia -: Continuous delivery and antiarrhythmic effect of an ε-protein kinase C-activating peptide [J].
Inagaki, K ;
Begley, R ;
Ikeno, F ;
Mochly-Rosen, D .
CIRCULATION, 2005, 111 (01) :44-50
[9]   Additive protection of the ischemic heart ex vivo by combined treatment with δ-protein kinase C inhibitor and ε-protein kinase C activator [J].
Inagaki, K ;
Hahn, HS ;
Dorn, GW ;
Mochly-Rosen, D .
CIRCULATION, 2003, 108 (07) :869-875
[10]   Acute protection of ischemic heart by FGF-2: involvement of FGF-2 receptors and protein kinase C [J].
Jiang, ZS ;
Padua, RR ;
Ju, HS ;
Doble, BW ;
Jin, Y ;
Hao, JM ;
Cattini, PA ;
Dixon, IMC ;
Kardami, E .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2002, 282 (03) :H1071-H1080