OXIDANT/ANTIOXIDANT EFFECTS OF TGF-B1 ON LUNG CELLS

描述：(根据申请者的抽象和具体目标改编。) 细胞因子转化生长因子-β1(TGF-β1) 与某些肺部疾病的发病机制有关 肺血管损伤和重塑。然而，它的机制是 对细胞的作用尚不清楚。该申请假设转化生长因子-β1 可能会影响肺血管系统，可能还会影响 肺内氧化/抗氧化系统的改变 细胞。具体目的是：1)评价“亲和力”的作用机制。 转化生长因子-β1对内皮细胞的氧化作用；2)测定血管内皮细胞 转化生长因子-β1降低细胞谷胱甘肽的机制；3)更好地定义 转化生长因子-β1对细胞内铜、锌、锰超氧化物歧化酶的调节作用 评估转化生长因子-β1使其氧化剂/抗氧化剂永久化的概念 通过自分泌作用对内皮细胞的影响 受细胞内谷胱甘肽含量的调节。这些研究可能会提供 转化生长因子-β1对肺血管内皮细胞作用的新认识 尤其是单元格，并且可以提供对 转化生长因子-β1对细胞的作用。它们也可能有助于更好地 从细胞水平认识某些肺的发病机制 以组织损伤和重塑为特征的疾病，从而导致 新的治疗方案。

DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) The cytokine transforming growth factor beta-1 (TGF-b1) has been implicated in the pathogenesis of certain lung diseases associated with pulmonary vascular injury and remodeling. However, its mechanism of action on cells is not known. The application hypothesizes that TGF-b1 may affect the pulmonary vasculature and possibly other components of the lung through alterations in oxidant/anti-oxidant systems within lung cells. The Specific Aims are to: 1) evaluate the mechanism of the "pro- oxidant" effect of TGF-b1 on endothelial cells; 2) determine the mechanism by which TGF-b1 reduces cellular glutathione; 3) better define the regulatory role of TGF-b1 on cellular Cu, Zn- and Mn-SOD; and 4) evaluate the concept that TGF-b1 perpetuates its oxidant/anti-oxidant effects on endothelial cells through an autocrine action that is regulated by the cellular glutathione content. The studies may provide new insights into the actions of TGF-b1 on pulmonary vascular endothelial cells, in particular, and may provide a broader interpretation of the action of TGF-b1 on cells in general. They may also help to better understand at the cellular level the pathogenesis of certain lung diseases characterized by tissue injury and remodeling, thereby leading to new therapeutic options.