Lipopolysaccharide-Induced Lysosomal Cell Death Through Reactive Oxygen Species in Rat Liver Cell Clone 9.

Autor: Hsu CS; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.; Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua, Taiwan., Chang SH; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan., Yang RC; Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua, Taiwan.; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan.; School of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan., Lee CH; Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua, Taiwan., Lee MS; Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua, Taiwan., Kao JK; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.; Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua, Taiwan.; School of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan., Shieh JJ; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.; Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
Jazyk: angličtina
Zdroj: Environmental toxicology [Environ Toxicol] 2024 Nov; Vol. 39 (11), pp. 5008-5018. Date of Electronic Publication: 2024 Jul 19.
DOI: 10.1002/tox.24377
Abstrakt: In sepsis, bacterial components, particularly lipopolysaccharide (LPS), trigger organ injuries such as liver dysfunction. Although sepsis induces hepatocyte damage, the mechanisms underlying sepsis-related hepatic failure remain unclear. In this study, we demonstrated that the LPS-treated rat hepatocyte cell line Clone 9 not only induced reactive oxygen species (ROS) generation and apoptosis but also increased the expression of the autophagy marker proteins LC3-II and p62, and decreased the expression of intact Lamp2A, a lysosomal membrane protein. Additionally, LPS increased lysosomal membrane permeability and galectin-3 puncta formation, and promoted lysosomal alkalization in Clone 9 cells. Pharmacological inhibition of caspase-8 and cathepsin D (CTSD) suppressed the activation of caspase-3 and rescued the viability of LPS-treated Clone 9 cells. Furthermore, LPS induced CTSD release associated with lysosomal leakage and contributed to caspase-8 activation. Pretreatment with the antioxidant N-acetylcysteine (NAC) not only diminished ROS generation and increased the cell survival rate, but also decreased the expression of activated caspase-8 and caspase-3 and increased the protein level of Lamp2A in LPS-treated Clone 9 cells. These results demonstrate that LPS-induced ROS causes lysosomal membrane permeabilization and lysosomal cell death, which may play a crucial role in hepatic failure in sepsis. Our results may facilitate the development of new strategies for sepsis management.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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