EC-SOD in Asbestos-Induced Lung Injury

EC-SOD 在石棉引起的肺损伤中的作用

• 批准号: 7118732
• 负责人: Roderick Jason Tan
• 金额: $ 4.08万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-13 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7118732
• 关键词: asbestos; cytoprotection; enzyme activity; extracellular matrix; genetic regulation; genetically modified animals; immunocytochemistry; laboratory mouse; lung injury; metalloendopeptidases; oxidative stress; peroxidation; pneumoconiosis; predoctoral investigator; superoxide dismutase; western blottings

DESCRIPTION (provided by applicant): Asbestosis is a debilitating interstitial lung disease caused by the inhalation of asbestos fibers and characterized by inflammation and fibrosis of alveolar interstitium. The pathogenesis of asbestosis is not fully understood, but reactive oxygen species (ROS) are thought to play a central role. Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the lung in other interstitial lung diseases but has not been studied in asbestos-mediated disease. The hypothesis of this proposal is that EC-SOD protects against asbestos-mediated lung injury by preventing oxidative damage and matrix metalloproteinase (MMP) activation. These studies will utilize biochemical and histological analyses to study the presence of EC-SOD in the lungs of asbestos- or control-treated mice. In addition, EC-SOD knockout and transgenic overexpressing mice will be treated with asbestos to determine if the presence of this antioxidant affects disease severity. Finally, experiments will examine whether the presence of EC-SOD affects activation of latent MMPs since these proteases can become activated by ROS and are known to contribute to disease progression in other models of pulmonary fibrosis.

描述（由申请人提供）：石棉是一种使石棉纤维吸入引起的衰弱的间质性肺疾病，其特征是肺泡间质的炎症和纤维化。石棉病的发病机理尚不完全了解，但是被动反应性氧（ROS）被认为起着核心作用。细胞外超氧化物歧化酶（EC-SOD）是一种抗氧化剂酶，可保护其他间质性肺部疾病中的肺部，但尚未在石棉介导的疾病中进行研究。该提议的假设是EC-SOD通过防止氧化损伤和基质金属蛋白酶（MMP）激活来预防石棉介导的肺损伤。这些研究将利用生化和组织学分析来研究石棉或对照处理的小鼠肺中EC-SOD的存在。此外，EC-SOD敲除和转基因过表达小鼠将用石棉处理，以确定这种抗氧化剂的存在是否会影响疾病的严重程度。最后，实验将检查EC-SOD的存在是否会影响潜在MMP的激活，因为这些蛋白酶可以被ROS激活，并且已知在其他肺纤维化模型中有助于疾病进展。