Thyroid hormone changes cardiomyocyte shape and geometry via ERK signaling pathway: potential therapeutic implications in reversing cardiac remodeling?
It has previously been shown that thyroid hormone can reverse cardiac remodeling in failing hearts by reducing myocardial wall stress due to the unique changes induced in cardiac myocyte shape. This effect may be of therapeutic relevance. Therefore, the present study has investigated potential signaling mechanisms underlying the thyroid hormone action on cardiac myocyte shape and geometry. Neonatal cardiomyocytes were treated with T(3) while untreated cells served as controls. T(3) administration for 48 h significantly increased the ratio of the major to minor cell axis and changed their shape from an almost circular to an elongated form. Cell area and protein synthesis were increased and T(3) treated cells expressed 51% alpha-MHC and 49% beta-MHC as compared to 100% beta-MHC expression in non-treated cells. This response was accompanied by a 1.9-fold increase in phospho-ERK levels early at 8 min which, within 60 min, returned to the levels of the untreated cells. Phospho-JNK levels were significantly reduced within 60 min after T(3) treatment while no changes in the expression of phospho-Akt and phospho-p38 MAPK were found between the T(3) treated and untreated cells. Administration of PD98059 (an inhibitor of ERK signaling) prevented the thyroid hormone induced changes in cardiomyocyte geometry and shape without a significant reduction in cell area and protein synthesis. In conclusion, T(3) induced changes in cardiomyocyte shape and geometry involve the ERK kinase signaling. This response is independent of the effects of T(3) on cell size and protein synthesis.
Pantos
C
C
Department of Pharmacology, University of Athens, 75 Mikras Asias Ave., Goudi 11527, Athens, Greece. cpantos@cc.uoa.gr
Xinaris
Christodoulos
C
Mourouzis
Iordanis
I
Malliopoulou
Vassiliki
V
Kardami
Elissavet
E
Cokkinos
Dennis V
DV
D000818:Animals; D000831:Animals, Newborn; D048430:Cell Shape / Q000187:drug effects*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005419:Flavonoids / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D014284:Triiodothyronine / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D005419:Flavonoids; D020033:Protein Isoforms; D014284:Triiodothyronine; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D009218:Myosins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one