Triiodothyronine induces over-expression of alpha-smooth muscle actin, restricts myofibrillar expansion and is permissive for the action of basic fibroblast growth factor and insulin-like growth factor I in adult rat cardiomyocytes.
Effects of triiodothyronine (T3) on the expression of cytoskeletal and myofibrillar proteins in adult rat cardiomyocytes (ARC) were followed during two weeks of culture in the presence of 20% T3-depleted (stripped) FCS. Control cultures expressed mainly beta-myosin heavy chain (MHC) mRNA. T3 caused a switch to alpha-MHC expression and a dose-dependent increase of alpha-smooth muscle (alpha-sm) actin mRNA and protein. In parallel, the number of alpha-sm actin immunoreactive cells increased from 1% in controls to 29 and 62% in ARC treated with 5 and 100 nM T3. In the presence of T3, cells exhibited a higher beating rate than controls. The distribution of myofibrils in T3-treated cells was restricted to the perinuclear area with a sharp boundary. Only 5% of the control cells but 30 and 62% of the T3-treated (5 and 100 nM) ARC showed this restricted myofibrillar phenotype. Basic fibroblast growth factor (bFGF) which restricts myofibrillar growth and upregulates alpha-sm actin in ARC cultured with normal FCS had no effect on alpha-sm actin in ARC cultured in stripped FCS, but potentiated the effect of T3. In contrast, insulin-like growth factor I (IGF I), which suppresses alpha-sm actin and stimulates myofibrillogenesis in the presence of normal FCS suppressed T3-induced alpha-sm actin expression in stripped FCS. Thus, T3 appears to be permissive for the action of bFGF and IGF I on alpha-sm actin expression.
Gosteli-Peter
M A
MA
Department of Internal Medicine, University Hospital Zurich, Switzerland.
Harder
B A
BA
Eppenberger
H M
HM
Zapf
J
J
Schaub
M C
MC
D000199:Actins / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009210:Myofibrils / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000494:pharmacology*
D000199:Actins; D012333:RNA, Messenger; D014284:Triiodothyronine; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I