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• W2066950983 abstract "Mitogenic growth factors and transforming growth factor β1 (TGF-β1) induce the generation of reactive oxygen species (ROS) in non-phagocytic cells, but their enzymatic source(s) and regulatory mechanisms are largely unknown. We previously reported on the ability of TGF-β1 to activate a cell surface-associated NADH:flavin: O2 oxidoreductase (NADH oxidase) that generates extracellular H2O2. In this study, we compared the ROS-generating enzymatic systems activated by mitogenic growth factors and TGF-β1 with respect to the primary reactive species produced (O2 vs. H2O2), the site of generation (intracellular vs. extracellular) and regulation by Ras. We find that the mitogenic growth factors PDGF-BB, FGF-2, and TGF-α (an EGF receptor ligand) are able to rapidly (within 5 min) induce the generation of intracellular O2 without detectable NADH oxidase activity or extracellular H2O2 release. In contrast, TGF-β1 does not stimulate intracellular O2 production and the delayed induction of extracellular H2O2 release is not associated with O2 production. Expression of dominant-negative Ras (N17Ras) protein by herpes simplex virus-mediated gene transfer blocks mitogen-stimulated intracellular O2 generation but has no effect on TGF-β1-induced NADH oxidase activation/H2O2 production. These results demonstrate that there are at least two distinctly different ROS-generating enzymatic systems in lung fibroblasts regulated by mitogenic growth factors and TGF-β1 via Ras-dependent and -independent mechanisms, respectively. In addition, these findings suggest that endogenous production of ROS by growth factors/ cytokines may have different biological effects depending on the primary reactive species generated and site of production.—Thannickal, V. J., Day, R. M., Klinz, S. G., Bastien, M. C., Larios, J. M., Fanburg, B. L. Ras-dependent and -independent regulation of reactive oxygen species by mitogenic growth factors and TGF-β1. FASEB J. 14, 1741–1748 (2000)" @default.
• W2066950983 created "2016-06-24" @default.
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• W2066950983 date "2000-09-01" @default.
• W2066950983 modified "2023-10-14" @default.
• W2066950983 title "Ras‐dependent and ‐independent regulation of reactive oxygen species by mitogenic growth factors and TGF‐β1" @default.
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• W2066950983 doi "https://doi.org/10.1096/fj.99-0878com" @default.
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