title: Thyroid hormone inhibition in L6 myoblasts of IGF-I-mediated glucose uptake and proliferation: new roles for integrin αvβ3.
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-[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 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.
authors.affiliation: Department of Sciences, University Roma Tre, Rome, Italy; sandra.incerpi@uniroma3.it.
authors.forename: Sandra
authors.initials: S
authors.lastname: Incerpi
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan;
authors.forename: Meng-Ti
authors.initials: MT
authors.lastname: Hsieh
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;
authors.forename: Hung-Yun
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan;
authors.forename: Guei-Yun
authors.initials: GY
authors.lastname: Cheng
authors.affiliation: Department of Biology, University Tor Vergata, Rome, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: De Vito
authors.affiliation: Department of Sciences, University Roma Tre, Rome, Italy;
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fiore
authors.affiliation: Department of Zoology, Beni-Suef University, Beni-Suef, Egypt;
authors.forename: R G
authors.initials: RG
authors.lastname: Ahmed
authors.affiliation: Department of Sciences, University Roma Tre, Rome, Italy;
authors.forename: Rosanna
authors.initials: R
authors.lastname: Salvia
authors.affiliation: Department of Sciences, University Roma Tre, Rome, Italy;
authors.forename: Elena
authors.initials: E
authors.lastname: Candelotti
authors.affiliation: Department of Sciences, University Roma Tre, Rome, Italy;
authors.forename: Stefano
authors.initials: S
authors.lastname: Leone
authors.affiliation: Department of Biology, University Tor Vergata, Rome, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Luly
authors.affiliation: Department of Biology, University Tor Vergata, Rome, Italy;
authors.forename: Jens Z
authors.initials: JZ
authors.lastname: Pedersen
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York;
authors.forename: Faith B
authors.initials: FB
authors.lastname: Davis
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York; Department of Medicine, Albany Medical College, Albany, New York.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013974:Thyroxine / Q000378:metabolism*
chemical_list: D039302:Integrin alphaVbeta3; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; D005947:Glucose; D013974:Thyroxine
keywords: extracellular regulated kinase 1/2; fluorescence-activated cell sorting; glucose transport; insulin-like growth factor type I; mitogen-activated protein kinase; phosphatidylinositol 3-kinase; tetraiodothyroacetic acid; thyroxine; triiodothyronine