caa a22 4500 445853379 CHVBK 20180317145420.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00204-010-0585-x doi (NATIONALLICENCE)springer-10.1007/s00204-010-0585-x Lipopolysaccharide induces apoptotic insults to human alveolar epithelial A549 cells through reactive oxygen species-mediated activation of an intrinsic mitochondrion-dependent pathway [Elektronische Daten] [Chi-Yuan Chuang, Ta-Liang Chen, Yih-Giun Cherng, Yu-Tyng Tai, Tyng-Guey Chen, Ruei-Ming Chen] Alveolar type II epithelial cells can regulate immune responses to sepsis-induced acute lung injury. Lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria, can cause septic shock. This study was designed to evaluate the cytotoxic effects of LPS on human alveolar epithelial A549 cells and its possible molecular mechanisms. Exposure of A549 cells to LPS decreased cell viability in concentration- and time-dependent manners. In parallel, LPS concentration- and time-dependently induced apoptosis of A549 cells. Meanwhile, LPS only at a high concentration of 10μg/ml caused mildly necrotic insults to A549 cells. In terms of the mechanism, exposure of A549 cells to LPS increased the levels of cellular nitric oxide and reactive oxygen species (ROS). Pretreatment with N-acetylcysteine (NAC), an antioxidant, significantly lowered LPS-caused enhancement of intracellular ROS in A549 cells and simultaneously attenuated the apoptotic insults. Sequentially, treatment of A549 cells with LPS caused significant decreases in the mitochondrial membrane potential and biosynthesis of adenosine triphosphate. In succession, LPS triggered the release of cytochrome c from the mitochondria to the cytoplasm. Activities of caspase-9 and caspase-6 were subsequently augmented following LPS administration. Consequently, exposure of A549 cells induced DNA fragmentation in a time-dependent manner. Pretreatment of A549 cells with NAC significantly ameliorated LPS-caused alterations in caspase-9 activation and DNA damage. Therefore, this study shows that LPS specifically induces apoptotic insults to human alveolar epithelial cells through ROS-mediated activation of the intrinsic mitochondrion-cytochrome c-caspase protease mechanism. Springer-Verlag, 2010 Alveolar epithelial cells nationallicence Lipopolysaccharide nationallicence Reactive oxygen species nationallicence Apoptosis nationallicence Intrinsic mechanism nationallicence Chuang Chi-Yuan Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan aut Chen Ta-Liang Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan aut Cherng Yih-Giun Department of Anesthesiology, Shuang Ho Hospital, Taipei, Taiwan aut Tai Yu-Tyng Cell Physiology and Molecular Image Research, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan aut Chen Tyng-Guey Cell Physiology and Molecular Image Research, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan aut Chen Ruei-Ming Cell Physiology and Molecular Image Research, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan aut Archives of Toxicology Springer-Verlag 85/3(2011-03-01), 209-218 0340-5761 85:3<209 2011 85 204 https://doi.org/10.1007/s00204-010-0585-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0585-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chuang Chi-Yuan Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan aut NATIONALLICENCE 700 1- Chen Ta-Liang Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan aut NATIONALLICENCE 700 1- Cherng Yih-Giun Department of Anesthesiology, Shuang Ho Hospital, Taipei, Taiwan aut NATIONALLICENCE 700 1- Tai Yu-Tyng Cell Physiology and Molecular Image Research, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan aut NATIONALLICENCE 700 1- Chen Tyng-Guey Cell Physiology and Molecular Image Research, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan aut NATIONALLICENCE 700 1- Chen Ruei-Ming Cell Physiology and Molecular Image Research, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/3(2011-03-01), 209-218 0340-5761 85:3<209 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer