title: Diverging antioxidative responses to IGF-1 in cultured human skin fibroblasts versus vascular endothelial cells.
abstract: Insulin-like growth factor 1 (IGF-1) stimulates cell proliferation and is crucial for maintenance of somatic tissues. However, this effect is associated with the inhibition of FOXO transcription factors and downregulation of antioxidative enzymes. In this study, we compared the responses of primary dermal fibroblasts and human umbilical vein endothelial cells with IGF-1 treatment. We found that IGF-1 primarily downregulated enzymatic antioxidants in skin fibroblasts. However, human umbilical vein endothelial cells were protected from an IGF-1-mediated decrease in antioxidative capacity. Moreover, IGF-1 also activated endothelial nitric oxide synthase in human umbilical vein endothelial cells. These observations suggest a dichotomous role for IGF-1, which provides for growth and repair needs of the soma, while attenuating the effect of oxidative stress on the vasculature by activating endothelial nitric oxide synthase. This increases the production of nitric oxide, an antiproliferative and, under certain circumstances, an antioxidant agent. Findings could help clarify the role of IGF-1 in aging and longevity of lower organisms, short-lived mammals, and humans.
authors.affiliation: The Center of Human Development and Aging, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA. stonerc@umdnj.edu
authors.forename: Rivka C
authors.initials: RC
authors.lastname: Stone
authors.forename: Soyeon
authors.initials: S
authors.lastname: Kim
authors.forename: Betsy J
authors.initials: BJ
authors.lastname: Barnes
authors.forename: Abraham
authors.initials: A
authors.lastname: Aviv
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007334:Insulin-Like Growth Factor I; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase