Artículo
Role of PTHrP in human intestinal Caco-2 cell response to oxidative stress
Fecha de publicación:
07/2013
Editorial:
Elsevier
Revista:
Biochimica Et Biophysica Acta-molecular Cell Research
ISSN:
0167-4889
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
We have previously demonstrated that parathyroid hormone (PTH) induces apoptosis in human colon adenocarcinoma Caco-2 cells but the effects of its tumoral analog PTH-related peptide (PTHrP) in this cell line are still unknown. In the present work we investigated whether PTHrP, as PTH, is able to induce Caco-2 cell apoptosis or if it exerts protective effects under apoptotic conditions. Using Caco-2 cells cultured under serum deprivation in the presence or absence of PTHrP we demonstrated that, differently to PTH, its analog employed at the same concentration (10− 8 M) is not a pro-apoptotic hormone. Cells were exposed to an oxidative insult in the form of hydrogen peroxide to induce apoptosis, which leads to a 50% loss of cell viability determined by MTS assay, morphological changes observed under fluorescence microscopy and Western blot analysis. Herein we demonstrate, for the first time, that pre-treatment with PTHrP prior to H2O2 incubation, prevents cell death induced by the apoptotic inductor; and using specific inhibitors we evidenced that protein kinase B (AKT), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2) and p38 mitogen-activated protein kinase (MAPK) mediate this anti-apoptotic effect. Also, we found that PTHrP decreases the pro-apoptotic protein BAX levels and increases the protein expression of the anti-apoptotic HSP27. Immunoblot analysis revealed that H2O2 increases the phosphorylation levels of AKT and MAPKs, exhibiting a cellular defense response; and consequently increases phospho-BAD levels. The H2O2-induced activation of protein kinases is reverted when cells are pre-treated with PTHrP. Altogether these results evidence a protective effect of PTHrP under apoptotic conditions in intestinal cells, which may be mediated by AKT and MAPKs.
Palabras clave:
Pthrp
,
Caco-2 Cell
,
Apoptosis
,
Mapk Akt
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CCT - BAHIA BLANCA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - BAHIA BLANCA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - BAHIA BLANCA
Articulos(INBIOSUR)
Articulos de INSTITUTO DE CIENCIAS BIOLOGICAS Y BIOMEDICAS DEL SUR
Articulos de INSTITUTO DE CIENCIAS BIOLOGICAS Y BIOMEDICAS DEL SUR
Citación
Lezcano, Virginia Alicia; Gentili, Claudia Rosana; Russo, Ana Josefa; Role of PTHrP in human intestinal Caco-2 cell response to oxidative stress; Elsevier; Biochimica Et Biophysica Acta-molecular Cell Research; 1833; 12; 7-2013; 2834-2843
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