title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University Hospital Zurich, Switzerland.
authors.forename: M A
authors.initials: MA
authors.lastname: Gosteli-Peter
authors.forename: B A
authors.initials: BA
authors.lastname: Harder
authors.forename: H M
authors.initials: HM
authors.lastname: Eppenberger
authors.forename: J
authors.initials: J
authors.lastname: Zapf
authors.forename: M C
authors.initials: MC
authors.lastname: Schaub
mesh_terms: 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*
chemical_list: D000199:Actins; D012333:RNA, Messenger; D014284:Triiodothyronine; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I