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

Autor: Paolo De Vito, Jens Z. Pedersen, Anna Maria Fiore, Paul J. Davis, Hung Yun Lin, Meng Ti Hsieh, Guei Yun Cheng, Elena Candelotti, Faith B. Davis, Rosanna Salvia, Paolo Luly, Rafay Ahmed, Sandra Incerpi, Stefano Leone
Rok vydání: 2014
Předmět:
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
medicine.medical_specialty
Physiology
Glucose uptake
Integrin
Biology
Settore BIO/09
Cell Line
Receptor
IGF Type 1
Myoblasts
Cell surface receptor
Internal medicine
medicine
Animals
Settore BIO/10
Insulin-Like Growth Factor I
Phosphorylation
Cell Proliferation
Mitogen-Activated Protein Kinase Kinases
Integrin alphaVbeta3
Triiodothyronine
Thyroid
Glucose transporter
Biological Transport
Cell Biology
Rats
Thyroxine
medicine.anatomical_structure
Endocrinology
Glucose
Gene Expression Regulation
biology.protein
Proto-Oncogene Proteins c-akt
Hormone
Signal Transduction
Zdroj: American journal of physiology. Cell physiology. 307(2)
ISSN: 1522-1563
Popis: 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 T4and IGF-I in rat L6 myoblasts, we have examined integrin αvβ3-mediated modulatory actions of T4on glucose uptake, measured through carrier-mediated 2-deoxy-[3H]-d-glucose uptake, and on cell proliferation stimulated by IGF-I, assessed by cell counting, [3H]-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 T4caused little or no cell proliferation but prevented both glucose uptake and proliferative actions of IGF-I. These actions of T4were mediated by an Arg-Gly-Asp (RGD)-sensitive pathway, suggesting the existence of crosstalk between IGFIR and the T4receptor located near the RGD recognition site on the integrin. An RGD-sequence-containing integrin inhibitor, a monoclonal antibody to αvβ3, and the T4metabolite tetraiodothyroacetic acid all blocked the inhibition by T4of 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 T4that modified the effects of IGF-I. We conclude that thyroid hormone inhibits IGF-I-stimulated glucose uptake and cell proliferation in L6 myoblasts.
Databáze: OpenAIRE
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