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Analysis of cellular senescence induced by lipopolysaccharide in pulmonary alveolar epithelial cells

Authors
 김창오 
Issue Date
2011
Description
Dept. of Medicine/박사
Abstract
There have been few studies on the relationship between senescence and acute infection, although immunosenescence has been recently introduced. In this work, it was examined the possibility of lipopolysaccharide (LPS) causing cellular senescence in lung alveolar epithelial cells. The morphologic and biochemical characteristics of senescence induced by LPS were analyzed. Then, it was clarifed how this cellular senescence phenomenon is associated with oxidative stress effect induced by LPS and whether antioxidants could inhibit reduced cellular viability by oxidant stress effect of LPS.Human-like type II lung epithelial cells (A549) were used. In cell viability using cell counting kit-8, exposure to LPS decreased cellular viability and induced growth arrest in a concentration-dependent manner. The pre-apoptotic concentration of LPS was determined by caspase activation using a Caspase-Glo 3/7 luminescence assay kit. This concentration of LPS caused morphologic characteristics shown in senescent cells and elevated senescence-associated β-galactosidase activity. In addition, lysosomal content associated with senescence was increased by LPS at the pre-apoptotic concentration. However, this concentration of LPS did not shorten the telomere length. Exposure to LPS resulted in the formation of hydrogen peroxide in a concentration-dependent manner. The ability of LPS to reduce cellular viability was inhibited by the presence of glutathione. This study revealed that LPS could induce cellular senescence in lung alveloar epithelial cells, and these phenomena were closely associated with hydrogen peroxide production by LPS. Taken together, it is suggested that LPS-induced cellular senescence may play an important role in limiting the tissue repair response after sepsis.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/133478
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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