Insulin-like growth factor-1 prevents Aβ[25-35] / (H2O2)-induced apoptosis in lymphocytes by reciprocal NF-κB activation and p53 inhibition via PI3K-dependent pathway

ABSTRACT The role of insulin-like growth factor (IGF-1) as neural survival factor for the treatment of Alzheimer’s disease has recently gained attention. The present study shows that IGF-1 protects lymphocytes from (10, 30 mM) Ab[25–35] and (25, 50, 100mM) H2O2-induced apoptosis through NF-kB activation and p53 down regulation involving the phosphoinositide 3-kinase (PI-3K)–dependent pathway as demonstrated by using either (25 mM) LY294002 (PI-3K inhibitor), (10 nM) ammonium pyrrolidinedithiocarbamate (PDTC; NF-kB inhibitor), 50 nM pifithrin-a (PFT; p53 inhibitor) or by using immunocytochemistry detection of NF-kB and p53 transcription factors activation. Importantly, IGF-1, PDTC and PFT were able to protect and rescue lymphocytes pre-exposed to 10 mM Ab[25–35], even when the three compounds were added up-to 12 h post- Ab[25–35] exposure. Altogether these results suggest that survival/rescue of lymphocytes from Ab[25–35] toxicity is determined by p53 inactivation via IGF-1/ PI-3K pathway.

• Autores: Jiménez del Río, Marlene; Vélez Pardo, Carlos Alberto
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2006
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/32449
• Acceso en línea: https://hdl.handle.net/10495/32449; https://www.tandfonline.com/doi/full/10.1080/08977190500361788?scroll=top&needAccess=true
• Palabra clave: Insulin-Like Growth Factor I; Factor I del Crecimiento Similar a la Insulina; Phosphatidylinositol 3-Kinases; Fosfatidilinositol 3-Quinasas; Apoptosis; Amyloid beta-Peptides; Péptidos beta-Amiloides; Hydrogen Peroxide; Peróxido de Hidrógeno; Tumor Suppressor Protein p53; Proteína p53 Supresora de Tumor
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc/2.5/co/