Effects of insulin-like growth factor-1 on rotenone-induced apoptosis in human lymphocyte cells.
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-kappaB, 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.
Avila-Gomez
Isabel Cristina
IC
School of Medicine, Medical Research Institute, Neuroscience Research Program, University of Antioquia, Medellin, Colombia.
Velez-Pardo
Carlos
C
Jimenez-Del-Rio
Marlene
M
D000328:Adult; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D012402:Rotenone / Q000633:toxicity*; D013481:Superoxides / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D061945:Caspase Inhibitors; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D012402:Rotenone; D013481:Superoxides; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases