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Effects of Insulin‐Like Growth Factor‐1 on Rotenone‐Induced Apoptosis in Human Lymphocyte Cells
Author(s) -
AvilaGomez Isabel Cristina,
VelezPardo Carlos,
JimenezDelRio Marlene
Publication year - 2010
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2009.00472.x
Subject(s) - rotenone , apoptosis , oxidative stress , microbiology and biotechnology , mitochondrion , dna fragmentation , depolarization , superoxide , reactive oxygen species , hydrogen peroxide , insulin , biology , programmed cell death , chemistry , biochemistry , endocrinology , enzyme
Human peripheral blood lymphocytes have been useful as a putative model of oxidative stress‐induced apoptosis for Parkinson’s disease. The present work shows that rotenone, a mitochondrial complex I inhibitor, induced time‐ and concentration‐dependent apoptosis in lymphocytes which was mediated by anion superoxide radicals (O 2 • − )/hydrogen peroxide, depolarization of mitochondria, caspase‐3 activation, concomitantly with the nuclear translocation of transcription factors such as NF‐κB, p53, c‐Jun and nuclei fragmentation. Since insulin‐like growth factor‐1 (IGF‐1) interferes with a cell’s apoptotic machinery when subjected to several stressful conditions, it is demonstrated here for the first time that IGF‐1 effectively protects lymphocytes against rotenone through PI‐3K/Akt activation, down‐regulation of p53 and maintenance of mitochondrial membrane potential independently of ROS generation. These data might contribute to understanding the role played by IGF‐1 against oxidative stress stimuli.