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Abstract:

The high incidence of obesity-related pathologies, led to the study of the mechanisms involved in preadipose cell proliferation and differentiation. Here, we demonstrate that modulation of erbB2, plays a fundamental role during proliferation and adipogenic induction of preadipocytes. Using 3T3-L1 cells as model, we demonstrate that EGF (10 nM, 5 min) in addition to stimulate receptor tyrosine phosphorylation of both erbB2 and EGFR, is able to induce the heterodimer erbB2-EGFR. We treated proliferating 3T3-L1 cells with two inhibitors, AG 825 (IC50 0.35 μM, 54 times more selective for erbB2 than for EGFR, IC50 19 μM), and AG 879 (IC50 of 1 μM for erbB2 versus 500 μM for EGFR). We found that both inhibited the proliferation on a dose-dependent basis, reaching a 30% maximal inhibition at 100 μM (P < 0.001) for AG825, and a 20% maximal inhibition at 10 μM (P < 0.001) for AG 879. These results involve erbB2 in 3T3-L1 proliferation. When studying the differentiation process, we found that the action of MIX-Dexa immediately activates MEK, JNK and p38 kinases. We observed that PD98059 and SP600125 (MEK-ERK and JNK inhibitors, respectively) added 1 h prior to the MIX-Dexa induction produced a decrease in erbB2 expression after 6 h, which is even greater than the one produced by the inducers, MIX-Dexa. This work supports erbB2 as a key factor in 3T3-L1 adipogenesis, acting mostly and not only during the proliferative phase but also during the differentiation through modulation of both its expression and activity. © 2007 Wiley-Liss, Inc.

Registro:

Documento: Artículo
Título:Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes
Autor:Pagano, E.; Coso, O.; Calvo, J.C.
Filiación:Laboratorio de Química de Proteoglicanos Y Matriz Extracelular, IByME, Buenos Aires, Argentina
IFIBYNE, Universidad de Buenos Aires, Facultad de Ciencias Exactas Y Naturales (FCEyN, UBA), Buenos Aires, Argentina
Department of Biological Chemistry, Universidad de Buenos Aires, Facultad de Ciencias Exactas Y Naturales (FCEyN, UBA), Buenos Aires, Argentina
Department of Molecular Biology
Laboratorio de Química de Proteoglicanos Y Matriz Extracelular, IByME, Vuelta de Obligado, 2490, (1428) Buenos Aires, Argentina
Palabras clave:3T3-L1; Adipogenesis; EGFR/erbB1; erbB2; Tyrphostin; 2 (2 amino 3 methoxyphenyl)chromone; 5 (2 benzothiazolyl)thiomethyl 4 hydroxy 3 methoxybenzylidenecyanoacetamide; anthra[1,9 cd]pyrazol 6(2h) one; dexamethasone; epidermal growth factor; epidermal growth factor receptor; epidermal growth factor receptor 2; heterodimer; isobutylmethylxanthine; mitogen activated protein kinase; mitogen activated protein kinase inhibitor; mitogen activated protein kinase kinase; mitogen activated protein kinase p38; protein tyrosine kinase; protein tyrosine kinase inhibitor; stress activated protein kinase; stress activated protein kinase inhibitor; tyrphostin; tyrphostin ag 879; unclassified drug; epidermal growth factor receptor; epidermal growth factor receptor 2; mitogen activated protein kinase; adipogenesis; animal cell; article; cell differentiation; cell proliferation; cell strain 3T3; controlled study; down regulation; embryo; functional proteomics; inhibition kinetics; mouse; nonhuman; priority journal; proadipocyte; protein expression; protein function; protein induction; protein phosphorylation; protein synthesis inhibition; adipocyte; animal; cytology; gene expression regulation; genetics; metabolism; physiology; 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Cell Differentiation; Cell Proliferation; Gene Expression Regulation; Mice; Mitogen-Activated Protein Kinases; Receptor, Epidermal Growth Factor; Receptor, erbB-2
Año:2008
Volumen:104
Número:1
Página de inicio:274
Página de fin:285
DOI: http://dx.doi.org/10.1002/jcb.21621
Título revista:Journal of Cellular Biochemistry
Título revista abreviado:J. Cell. Biochem.
ISSN:07302312
CODEN:JCEBD
CAS:2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; anthra[1,9 cd]pyrazol 6(2h) one, 129-56-6; dexamethasone, 50-02-2; epidermal growth factor, 59459-45-9, 62229-50-9; epidermal growth factor receptor, 79079-06-4; epidermal growth factor receptor 2, 137632-09-8; isobutylmethylxanthine, 28822-58-4; mitogen activated protein kinase, 142243-02-5; mitogen activated protein kinase kinase, 142805-58-1; protein tyrosine kinase, 80449-02-1; stress activated protein kinase, 155215-87-5; mitogen activated protein kinase, 142243-02-5; Mitogen-Activated Protein Kinases, EC 2.7.1.37; Receptor, Epidermal Growth Factor, EC 2.7.1.112; Receptor, erbB-2, EC 2.7.1.112
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07302312_v104_n1_p274_Pagano

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Citas:

---------- APA ----------
Pagano, E., Coso, O. & Calvo, J.C. (2008) . Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes. Journal of Cellular Biochemistry, 104(1), 274-285.
http://dx.doi.org/10.1002/jcb.21621
---------- CHICAGO ----------
Pagano, E., Coso, O., Calvo, J.C. "Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes" . Journal of Cellular Biochemistry 104, no. 1 (2008) : 274-285.
http://dx.doi.org/10.1002/jcb.21621
---------- MLA ----------
Pagano, E., Coso, O., Calvo, J.C. "Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes" . Journal of Cellular Biochemistry, vol. 104, no. 1, 2008, pp. 274-285.
http://dx.doi.org/10.1002/jcb.21621
---------- VANCOUVER ----------
Pagano, E., Coso, O., Calvo, J.C. Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes. J. Cell. Biochem. 2008;104(1):274-285.
http://dx.doi.org/10.1002/jcb.21621