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 μM) Aβ[_25–35] and (25, 50, 100 μM) H₂O₂-induced apoptosis through NF-κB activation and p53 down regulation involving the phosphoinositide 3-kinase (PI-3K)–dependent pathway as demonstrated by using either (25 μM) LY294002 (PI-3K inhibitor), (10 nM) ammonium pyrrolidinedithiocarbamate (PDTC; NF-κB inhibitor), 50 nM pifithrin-α (PFT; p53 inhibitor) or by using immunocytochemistry detection of NF-κB and p53 transcription factors activation. Importantly, IGF-1, PDTC and PFT were able to protect and rescue lymphocytes pre-exposed to 10 μM Aβ[_25–35], even when the three compounds were added up-to 12 h post- Aβ[_25–35] exposure. Altogether these results suggest that survival/rescue of lymphocytes from Aβ[_25–35] toxicity is determined by p53 inactivation via IGF-1/ PI-3K pathway.

• Beta-amyloid
• H₂O₂
• IGF-1
• NF-κB
• PI-3K
• p53