Ras-dependent and -independent regulation of reactive oxygen species by mitogenic growth factors and TGF-beta1.
Ras-dependent and -independent regulation of reactive oxygen species by mitogenic growth factors and TGF-beta1.
复制标题
有丝分裂生长因子和 TGF-β1 对活性氧的 Ras 依赖性和非依赖性调节。
DOI：
10.1096/fj.99-0878com
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Fanburg,BL
中科院分区：
文献类型：
--
作者：
Thannickal,VJ;Day,RM;Klinz,SG;Bastien,MC;Larios,JM;Fanburg,BL
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: O2oxidoreductase (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 (O2vs. 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 O2without detectable NADH oxidase activity or extracellular H2O2release. In contrast, TGF‐β1 does not stimulate intracellular O2production and the delayed induction of extracellular H2O2release is not associated with O2production. Expression of dominant‐negative Ras (N17Ras) protein by herpes simplex virus‐mediated gene transfer blocks mitogen‐stimulated intracellular O2generation but has no effect on TGF‐β1‐induced NADH oxidase activation/H2O2production. 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)
