Influence of fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-I) on cytoskeletal and contractile structures and on atrial natriuretic factor (ANF) expression in adult rat ventricular cardiomyocytes in culture.
The effects of basic fibroblast growth factor (bFGF) and of insulin-like growth factor-I (IGF-I) on structural (actin cytoskeleton and myofibrillar apparatus) remodeling and on the expression of atrial natriuretic factor (ANF) in adult rat ventricular cardiomyocytes have been followed during the hypertrophy reaction up to 3 weeks in culture. Cells attach to the substratum spread into polygonal shapes with pseudopodia and resume contractile function after 1 week. A well structured actin cytoskeleton with stress fiber-like structures fills the cell bodies and the extensions. In controls and with IGF-I cells grow to the double volume while bFGF induces a four-fold increase. The myofibrillar apparatus follows the actin stress fiber-like structures in growing out into the cell periphery. Immunoreactive ANF granules develop and are concentrated around the nuclear region. The fetally occurring alpha-smooth muscle actin (alpha-sm-actin) is re-expressed in stress fiber-like structures. IGF-I down-regulates alpha-sm-actin and ANF and promotes myofibrillar growth whereas bFGF has the opposite effect by up-regulating alpha-sm-actin (on average five to six times more than in controls as analysed by immunoblotting) and ANF. In addition, bFGF restricts myofibrillar growth with a sharp boundary in the perinuclear region. The most dense packing of alpha-sm-actin in the cytoskeleton is found just outside the area containing the myofibrils; so alpha-sm-actin seems to restrict myofibrillar assembly and growth. These cells are nevertheless beating like the controls. The relative increase of cytoskeletal structures with the concomitant lack of growth of myofibrils, is mostly due to an increase in alpha-sarcomeric actin (alpha-cardiac and alpha-skeletal muscle actin) and in alpha-sm-actin.
Harder
B A
BA
Institute of Pharmacology, University of Zurich, Switzerland.
Schaub
M C
MC
Eppenberger
H M
HM
Eppenberger-Eberhardt
M
M
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006352:Heart Ventricles; D015151:Immunoblotting; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; C472610:atrial natriuretic peptide, rat; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D009320:Atrial Natriuretic Factor