Effect of inflammation and iron overload on nitric oxide production, iron sulfur protein biosynthesis and cell apoptosis in BV2 microglia cell

• Main Authors: Jiang, Zonghan, 姜宗翰
• Other Authors: Liew, Yihfong
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/49773515298157999404

碩士 === 輔仁大學 === 營養科學系 === 100 === Abstract Micoglia cell plays an important role in many neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. It is been found that massive amyloid plaque accumulated in patients’ brain in Alzheimer’s diseases which accompanied with iron overload. However iron overload affects inflammation response to iron-sulfur protein regulation and apoptosis in micoglia cell is not well documented. Our study is willing to find out the effects of iron overload and inflammation on iron-sulfur protein biosynthesis, tRNA thio-modification and cell apoptosis in microglia cell. LPS + IFN-γ treatment aggressively up regulated nitric oxide secretion in microglia cell. LPS + IFN-γ treatment reduced c-aconitase, m-aconitase and SDH enzyme activities, also reduced the expressions of iron-sulfur cluster synthesis protein, IscS and cytosol tRNA thio-modification. Furthermore, LPS+IFN-γ increased the phosphorylation of mTOR protein and the mRNA expression of XBP1 and CHOP. Meanwhile, it also reduced the cell survival rate about 30%. On the other hand, LPS + IFN-γ co-treated with iron overload reduced the secretion of nitric oxide, but treated with iron overload did not affect any iron-sulfur protein synthesis and cell apoptosis. Above all, inflammation treatment decreased mitochondria IscS protein which resulted in iron-sulfur cluster synthesis insufficiency. This progress cut down the iron-sulfur protein enzyme activities and limited tRNA thio-modifications. Inflammation facilitated cell apoptosis through ER stresss in microglia cell. Supposed, LPS + IFN-γ induced inflammation destructed the mitochondria function and raised ER stress is associated with cell apoptosis in microglia cell.