Thyroid hormone activates Akt and prevents serum starvation-induced cell death in neonatal rat cardiomyocytes.
Thyroid hormone is known to cause hypertrophy, tachycardia, vasorelaxation, and enhanced contractile function. The exact mechanisms responsible for these effects are unknown but classical regulation of gene expression through binding to nuclear receptors has been widely implicated. Data have also accumulated suggesting that TH can exert effects through non-classical mechanisms involving activation of signal transduction pathways. Whether thyroid hormone can activate signal transduction pathways in the heart is unknown. In this study, we treated neonatal rat cardiomyocytes with T3 and determined the expression and phosphorylation of signaling molecules. T3 caused specific activation of Akt/PKB signaling after 24 h of treatment. Since Akt is known to protect against cell death, cells were serum-starved in the presence or absence of T3 to determine whether T3 could protect against serum starvation-induced cell death. Indeed, myocytes treated with T3 displayed enhanced sarcomeric structure after 4 days of serum starvation. T3 increased cell viability as measured by MTT assays, prevented DNA laddering, and reduced TUNEL positive cells, which was associated with increased phosphorylated Akt and glycogen synthase kinase 3beta (GSK-3beta). The protective effect of T3 on cell viability, DNA laddering and TUNEL positive cells were blocked by LY294002, a phosphoinositide-3 kinase (PI3K) inhibitor that blocks Akt signaling. Overall these data suggest that T3 can activate Akt in cardiomyocytes which protects myocytes against cell death.
Kuzman
James A
JA
Cardiovascular Research Institute, University of South Dakota School of Medicine and South Dakota Health Research Foundation, 1100 East 21st Street-Suite 700, Sioux Falls, SD 57105, USA.
Gerdes
A Martin
AM
Kobayashi
Satoru
S
Liang
Qiangrong
Q
D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology*
D002867:Chromones; D016895:Culture Media, Serum-Free; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014284:Triiodothyronine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt