Non-genomic effects of thyroid hormone in adult cardiac myocytes: relevance to gene expression and cell growth

作者：Iordanidou Anna; Hadzopoulou Cladaras Margarita; Lazou Antigone^*

来源：Molecular and Cellular Biochemistry, 2010, 340(1-2): 291-300.

DOI：10.1007/s11010-010-0430-9

• Adult cardiac myocytes
• Thyroid hormone
• Non-genomic action
• Intracellular signalling pathways
• Hypertrophy
• SERCA
• MHC

Besides the well-characterized genomic action of thyroid hormone (TH), mediated by thyroid hormone receptors (TRs), accumulating data support the so-called non-genomic action of TH, which is often related to activation of signalling pathways. In this study, we sought to determine whether TH activates intracellular signalling pathways in the adult cardiac myocytes and whether such activation modulates cell growth and the expression of target proteins important in cardiac function. We demonstrate that TH promotes a rapid increase in the phosphorylation of several kinases, ERK1/2, PKC delta, p38-MAPK and Akt. This activation is inhibited by triiodothyroacetic acid (triac), which is a TH analogue known to displace the hormone from membrane bound receptors, indicating that this TH effect is mediated through a cell membrane-initiated mechanism. Furthermore, using specific inhibitors of the TH-activated kinases, we show that the long-term effects of TH on the expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), alpha- and beta-myosin heavy chain (MHC) and cell growth are reverted, implying that what is initiated as a non-genomic action of the hormone interfaces with genomic effects. These data provide further insights into the underlying mechanisms of TH action in the heart with potentially important implications in the management of cardiac pathology.

• 出版日期2010-7