Adult cardiomyocytes express functional high-affinity receptors for basic fibroblast growth factor.
As a first step in addressing the question of function for basic fibroblast growth factor (bFGF) in the adult myocardium, expression of bFGF receptors by adult rat myocytes was investigated. Cross-linking of 125I-labeled bFGF to purified sarcolemmal vesicles from adult hearts indicated specific binding to 90- to 104-kDa proteins, whereas equilibrium binding studies revealed the presence of "low"-affinity (1 nM) and "high"-affinity (115 pM) sites. Adult myocytes were found to express short and long variants of bFGF receptor 1 (FGFR-1, tyrosine kinase) mRNA. Adult heart overall levels of FGFR-1 mRNA were decreased by about one-third of corresponding fetal values. Several lines of evidence indicated that bFGF receptors in adult cardiomyocytes in situ and/or in isolation are functional. Isolated adult myocytes were found to be capable of heparin-resistant internalization of 125I-labeled bFGF, to lose their viability after interaction with bFGF-saporin (a mitotoxin known to kill cells after entry via the bFGF receptor), and to respond to bFGF by activation of mitogen-activated protein kinase. In addition, introduction of exogenous bFGF into the myocardium by Langendorff perfusion resulted in stimulation of tyrosine phosphorylation in association with cardiomyocyte intercalated disks, as assessed by immunofluorescence. It is concluded that adult cardiomyocytes express functionally coupled high-affinity bFGF receptors and that they are capable of a biologic response to bFGF in vivo.
Liu
L
L
St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Pasumarthi
K B
KB
Padua
R R
RR
Massaeli
H
H
Fandrich
R R
RR
Pierce
G N
GN
Cattini
P A
PA
Kardami
E
E
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D016922:Cellular Senescence; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015870:Gene Expression; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism
D015335:Molecular Probes; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D014443:Tyrosine; D017871:Calcium-Calmodulin-Dependent Protein Kinases