title: Overstimulation can create health problems due to increases in PI3K/Akt/GSK3 insensitivity and GSK3 activity.
abstract: Aging is linked to decrease of the body cell use of growth hormone (GH) and thyroxine, whereas the decrease is via "death hormones" inhibition? This study proposes different viewpoints. Since interleukin 17 receptor C (IL17RC) is highly expressed in tissues from age-related macular degeneration (AMD) patients, IL17RC signaling pathways are explored to evaluate Wnts/vascular endothelial growth factor (VEGF) expression and complement activity, which are pathological factors in AMD. IL17RC overexpression or VEGF treatment was performed in two cell lines for up to two-day. Real-time Quantitative PCR, confocal microscopy, immune-blot, MTT assay, etc. measured downstream effects. IL17RC overexpression increases Wnts and VEGF that forms complexes with Wnt-signaling components. VEGF or the Wnt-signaling components interacting with C3 suggests alternative complement pathway activation. Moreover, IL17RC-overexpressed cells or VEGF-treated cells for two-day, which is overstimulation, increase PI3K/Akt/GSK3 insensitivity and GSK3 activity, and decrease growth/survival. High GSK3 activity associates with many chronic diseases including type II Diabetes. This study shows high GSK3 activity can result from PI3K/Akt overstimulation. Type II Diabetes shows insulin resistance that the body cells decrease insulin use. Possessing little sensitive PI3K/Akt for receptor activation, cells after overstimulation, although live, hardly respond to PI3K/Akt activators including GH, thyroxine and insulin. These results suggest an alternative explanation of the body cells declining hormone use since various kinds of cell signaling-induced overstimulation events almost always linked to PI3K/Akt, increase with age. Playing pathological roles in senescence and diseases, overstimulation eventually generates health problems.
authors.affiliation: Intramural Research Program, National Center for Complementary and Alternative Medicine, US Department of Health and Human Services, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Xunxian
authors.initials: X
authors.lastname: Liu
keywords: AMD; Aging; Complement; Death hormones; IL17/IL17RC; Insensitivity; PI3K/Akt/GSK3/GSK3 substrates; Signaling; VEGF
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