Thyroid hormone stimulates Na(+)-Ca2+ exchanger expression in rat cardiac myocytes.
We investigated whether thyroid hormone directly affects Na(+)-Ca2+ exchanger expression in cardiac myocytes. Cultured neonatal rat cardiocytes were prepared from 1-day-old Sprague-Dawley rats. Intracellular Na+ concentration ([Na+]i) in cardiocytes was measured by using the Na(+)-sensitive dye sodium-binding benzofran isophthalate (SBFI). Na(+)-Ca2+ exchanger messenger RNA (mRNA) and protein expression were assayed by Northern and Western blotting, respectively. Triiodothyronine (T3; 10(-8) M) showed no effect on [Na+]i in cardiocytes, whereas ouabain (100 microM) caused a significant increase in [Na+]i from 11.3 +/- 5.0 to 21.8 +/- 5.0 mM. Exposure of cardiocytes to ouabain caused a rapid increase in Na(+)-Ca2+ exchanger mRNA accumulation, with a maximal twofold elevation at 12 h. The ouabain-induced Na(+)-Ca2+ exchanger mRNA accumulation was still observed in the Ca(2+)-free culture medium. On the other hand, exposure of cardiocytes to T3 induced a gradual increase in Na+ exchanger mRNA accumulation, with a maximal threefold increase at 24 h. Even in Na(+)-free medium, T3 still induced a twofold increase in Na(+)-Ca2+ exchanger mRNA accumulation in cardiocytes. Exposure of cardiocytes to T3 for 24-48 h also caused a marked increase in Na(+)-Ca2+ exchanger protein accumulation. In conclusion, thyroid hormone directly increases cardiac Na(+)-Ca2+ exchanger expression, independent of alterations in Na+ mobilization. These findings suggest also that thyroid hormone and Na+ regulate Na(+)-Ca2+ exchanger gene expression through distinct molecular regulatory pathways.
Hojo
Y
Y
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Ikeda
U
U
Tsuruya
Y
Y
Ebata
H
H
Murata
M
M
Okada
K
K
Saito
T
T
Shimada
K
K
D000818:Animals; D000831:Animals, Newborn; D017920:Antiporters / Q000096:biosynthesis* / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D014284:Triiodothyronine / Q000494:pharmacology*
D017920:Antiporters; D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D014284:Triiodothyronine; D010042:Ouabain; D012964:Sodium