ABSTRACT Cellular behavior can be considered to be the result of a very complex spatial and temporal integration of intracellular and extracellular signals. These signals arise from serum-soluble factors as well as from cell–substrate or cell–cell interactions. The current approach in mitogenesis studies is generally to analyze the effect of a single growth factor on serum-starved cells. In this context, a metabolic hormone such as insulin is found to be a mitogenic agent in many cellular types. In the present study, we have considered the effect of insulin stimulation in platelet-derived growth factor (PDGF)-activated NIH-3T3 and C2C12 cells. Our results show that insulin is able to inhibit strongly both NIH-3T3 and C2C12 cell growth induced by PDGF, one of the most powerful mitotic agents for these cell types. This inhibitory effect of insulin is due primarily to a premature down-regulation of the PDGF receptor. Thus, when NIH-3T3 or C2C12 cells are stimulated with both PDGF and insulin, we observe a decrease in PDGF receptor phosphorylation with respect to cells treated with PDGF alone. In particular, we find that costimulation with insulin leads to a reduced production of H2O2 with respect to cell stimulation with PDGF alone. The relative low concentration of H2O2 in PDGF/insulin-costimulated cell leads to a limited down-regulation of protein tyrosine phosphatases, and, consequently, to a reduced PDGF receptor phosphorylation efficiency. The latter is very likely to be responsible for the insulin-dependent inhibition of PDGF-receptor mitogenic signaling.

INSULIN INHIBITS PLATELET-DERIVED GROWTH FACTOR-INDUCED CELL PROLIFERATION / P. CIRRI; M. TADDEI; P. CHIARUGI; F. BURICCHI; A. CASELLI; P. PAOLI; E. GIANNONI; G. CAMICI; G. MANAO; G. RAUGEI; G. RAMPONI. - In: MOLECULAR BIOLOGY OF THE CELL. - ISSN 1059-1524. - STAMPA. - 16:(2005), pp. 73-83. [10.1091/mbc.E04-01-0011]

INSULIN INHIBITS PLATELET-DERIVED GROWTH FACTOR-INDUCED CELL PROLIFERATION

CIRRI, PAOLO;TADDEI, MARIA LETIZIA;CHIARUGI, PAOLA;CASELLI, ANNA;PAOLI, PAOLO;GIANNONI, ELISA;CAMICI, GUIDO;MANAO, GIAMPAOLO;RAUGEI, GIOVANNI;RAMPONI, GIAMPIETRO
2005

Abstract

ABSTRACT Cellular behavior can be considered to be the result of a very complex spatial and temporal integration of intracellular and extracellular signals. These signals arise from serum-soluble factors as well as from cell–substrate or cell–cell interactions. The current approach in mitogenesis studies is generally to analyze the effect of a single growth factor on serum-starved cells. In this context, a metabolic hormone such as insulin is found to be a mitogenic agent in many cellular types. In the present study, we have considered the effect of insulin stimulation in platelet-derived growth factor (PDGF)-activated NIH-3T3 and C2C12 cells. Our results show that insulin is able to inhibit strongly both NIH-3T3 and C2C12 cell growth induced by PDGF, one of the most powerful mitotic agents for these cell types. This inhibitory effect of insulin is due primarily to a premature down-regulation of the PDGF receptor. Thus, when NIH-3T3 or C2C12 cells are stimulated with both PDGF and insulin, we observe a decrease in PDGF receptor phosphorylation with respect to cells treated with PDGF alone. In particular, we find that costimulation with insulin leads to a reduced production of H2O2 with respect to cell stimulation with PDGF alone. The relative low concentration of H2O2 in PDGF/insulin-costimulated cell leads to a limited down-regulation of protein tyrosine phosphatases, and, consequently, to a reduced PDGF receptor phosphorylation efficiency. The latter is very likely to be responsible for the insulin-dependent inhibition of PDGF-receptor mitogenic signaling.
2005
16
73
83
P. CIRRI; M. TADDEI; P. CHIARUGI; F. BURICCHI; A. CASELLI; P. PAOLI; E. GIANNONI; G. CAMICI; G. MANAO; G. RAUGEI; G. RAMPONI
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/26593
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