Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Arch Gerontol Geriatr. 2012 Mar-Apr;54(2):e35-41. doi: 10.1016/j.archger.2011.07.016. Epub 2011 Aug 25.
In this work, it was examined the possibility of lipopolysaccharide (LPS) causing cellular senescence in lung alveolar epithelial cells. Then, it was clarified 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. 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.
本研究旨在探讨脂多糖（LPS）是否会导致肺肺泡上皮细胞发生细胞衰老。然后，阐明了 LPS 诱导的细胞衰老现象与氧化应激效应之间的关系，以及抗氧化剂是否可以抑制 LPS 氧化应激效应对细胞活力的降低。在使用细胞计数试剂盒-8 的细胞活力测定中，LPS 的暴露以浓度依赖性方式降低了细胞活力并诱导了生长停滞。使用 Caspase-Glo 3/7 发光测定试剂盒通过半胱天冬酶激活来确定 LPS 的凋亡前浓度。该浓度的 LPS 引起了与衰老细胞相似的形态特征，并提高了衰老相关的β-半乳糖苷酶活性。此外，LPS 在凋亡前浓度下增加了与衰老相关的溶酶体含量。然而，该浓度的 LPS 并没有缩短端粒长度。LPS 的暴露以浓度依赖性方式导致过氧化氢的形成。LPS 降低细胞活力的能力被谷胱甘肽所抑制。本研究表明，LPS 可诱导肺肺泡上皮细胞发生细胞衰老，这些现象与 LPS 产生的过氧化氢密切相关。综上所述，提示 LPS 诱导的细胞衰老可能在限制脓毒症后组织修复反应中发挥重要作用。
