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Insulin‐like growth factor‐1 prevents Amyloid beta[25–35]/ (H2O2)‐ induced apoptosis in lymphocytes by reciprocal NF‐kappa‐B activation and p53 inhibition via PI3K‐dependent pathway
Author(s) -
VelezPardo Carlos,
Del Rio Marlene Jimenez
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb71-a
Subject(s) - intracellular , apoptosis , insulin like growth factor , ly294002 , transcription factor , nfkb1 , growth factor , pi3k/akt/mtor pathway , signal transduction , oxidative stress , kinase , microbiology and biotechnology , biology , chemistry , pharmacology , medicine , cancer research , endocrinology , biochemistry , receptor , gene
The role of insulin‐like growth factor (IGF‐1) as neural survival factor for the treatment of Alzheimer's disease has recently gained attention. However, the detailed intracellular mechanism involved in this effect remains to be fully elucidated. The present study shows that IGF‐1 protects peripheral blood lymphocytes (PBL) from (10, 30 μM) Aβ[ 25–35 ] and (25, 50, 100 μM) H 2 O 2 ‐induced apoptosis through NF‐κB activation and p53 down regulation via (PI) 3‐kinase (PI‐3K)–dependent pathway as demonstrated by using either specific (25 μM) LY294002 (PI‐3K inhibitor), (10nM) ammonium pyrrolidinedithiocarbamate (PDTC; NF‐κB inhibitor), 50nM 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 10μM Aβ[ 25–35 ], even when the three compounds were added up‐to 12 h post‐ Aβ[ 25–35 ] exposure. These results suggest that survival/rescue of lymphocytes from Aβ[ 25–35 ] toxicity is determined by p53 inactivation via IGF‐1/ PI‐3K pathway. These data may contribute to a better understanding of the intracellular molecular mechanism by which IGF‐1 promotes cell survival against oxidative stress stimuli.