Thyroid hormones l-thyroxine (T4) and 3,3',5-triiodo-l-thyronine (T3) have been shown to initiate short- and long-term effects via a plasma membrane receptor site located on integrin αvβ3. Also insulin-like growth factor type I (IGF-I) activity is known to be subject to regulation by this integrin. To investigate the possible cross-talk between T4 and IGF-I in rat L6 myoblasts, we have examined integrin αvβ3-mediated modulatory actions of T4 on glucose uptake, measured through carrier-mediated 2-deoxy-[(3)H]-d-glucose uptake, and on cell proliferation stimulated by IGF-I, assessed by cell counting, [(3)H]-thymidine incorporation, and fluorescence-activated cell sorting analysis. IGF-I stimulated glucose transport and cell proliferation via the cell surface IGF-I receptor (IGFIR) and, downstream of the receptor, by the phosphatidylinositol 3-kinase signal transduction pathway. Addition of 0.1 nM free T4 caused little or no cell proliferation but prevented both glucose uptake and proliferative actions of IGF-I. These actions of T4 were mediated by an Arg-Gly-Asp (RGD)-sensitive pathway, suggesting the existence of crosstalk between IGFIR and the T4 receptor located near the RGD recognition site on the integrin. An RGD-sequence-containing integrin inhibitor, a monoclonal antibody to αvβ3, and the T4 metabolite tetraiodothyroacetic acid all blocked the inhibition by T4 of IGF-I-stimulated glucose uptake and cell proliferation. Western blotting confirmed roles for activated phosphatidylinositol 3-kinase and extracellular regulated kinase 1/2 (ERK1/2) in the effects of IGF-I and also showed a role for ERK1/2 in the actions of T4 that modified the effects of IGF-I. We conclude that thyroid hormone inhibits IGF-I-stimulated glucose uptake and cell proliferation in L6 myoblasts.

Incerpi, S., Hsieh, M., Lin, H., Cheng, G., DE VITO, P., Fiore, A., et al. (2014). Thyroid hormone inhibition in L6 myoblasts of IGF-I-mediated glucose uptake and proliferation: new roles for integrin αvβ3. AMERICAN JOURNAL OF PHYSIOLOGY. CELL PHYSIOLOGY, 307(2), C150-C161 [10.1152/ajpcell.00308.2013].

Thyroid hormone inhibition in L6 myoblasts of IGF-I-mediated glucose uptake and proliferation: new roles for integrin αvβ3

DE VITO, PAOLO;LULY, PAOLO;PEDERSEN, JENS ZACHO;
2014-07-15

Abstract

Thyroid hormones l-thyroxine (T4) and 3,3',5-triiodo-l-thyronine (T3) have been shown to initiate short- and long-term effects via a plasma membrane receptor site located on integrin αvβ3. Also insulin-like growth factor type I (IGF-I) activity is known to be subject to regulation by this integrin. To investigate the possible cross-talk between T4 and IGF-I in rat L6 myoblasts, we have examined integrin αvβ3-mediated modulatory actions of T4 on glucose uptake, measured through carrier-mediated 2-deoxy-[(3)H]-d-glucose uptake, and on cell proliferation stimulated by IGF-I, assessed by cell counting, [(3)H]-thymidine incorporation, and fluorescence-activated cell sorting analysis. IGF-I stimulated glucose transport and cell proliferation via the cell surface IGF-I receptor (IGFIR) and, downstream of the receptor, by the phosphatidylinositol 3-kinase signal transduction pathway. Addition of 0.1 nM free T4 caused little or no cell proliferation but prevented both glucose uptake and proliferative actions of IGF-I. These actions of T4 were mediated by an Arg-Gly-Asp (RGD)-sensitive pathway, suggesting the existence of crosstalk between IGFIR and the T4 receptor located near the RGD recognition site on the integrin. An RGD-sequence-containing integrin inhibitor, a monoclonal antibody to αvβ3, and the T4 metabolite tetraiodothyroacetic acid all blocked the inhibition by T4 of IGF-I-stimulated glucose uptake and cell proliferation. Western blotting confirmed roles for activated phosphatidylinositol 3-kinase and extracellular regulated kinase 1/2 (ERK1/2) in the effects of IGF-I and also showed a role for ERK1/2 in the actions of T4 that modified the effects of IGF-I. We conclude that thyroid hormone inhibits IGF-I-stimulated glucose uptake and cell proliferation in L6 myoblasts.
15-lug-2014
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/09 - FISIOLOGIA
Settore BIO/10 - BIOCHIMICA
English
phosphatidylinositol 3-kinase; triiodothyronine; fluorescence-activated cell sorting; extracellular regulated kinase 1/2; mitogen-activated protein kinase; glucose transport; thyroxine; tetraiodothyroacetic acid; insulin-like growth factor type I
Incerpi, S., Hsieh, M., Lin, H., Cheng, G., DE VITO, P., Fiore, A., et al. (2014). Thyroid hormone inhibition in L6 myoblasts of IGF-I-mediated glucose uptake and proliferation: new roles for integrin αvβ3. AMERICAN JOURNAL OF PHYSIOLOGY. CELL PHYSIOLOGY, 307(2), C150-C161 [10.1152/ajpcell.00308.2013].
Incerpi, S; Hsieh, M; Lin, H; Cheng, G; DE VITO, P; Fiore, A; Ahmed, R; Salvia, R; Candelotti, E; Leone, S; Luly, P; Pedersen, Jz; Davis, F; Davis, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/88768
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