title: Lysosome dysfunction enhances oxidative stress-induced apoptosis through ubiquitinated protein accumulation in Hela cells.
abstract: The role of lysosomal system in oxidative stress-induced apoptosis in cancer cells is not fully understood. Menadione is frequently used as oxidative stress model. It is indicated that menadione could induce autophagy in Hela cells. In the present study, we examined whether the lysosomal inhibitor, ammonium chloride (NH(4)Cl) could prevent the autophagy flux by inhibiting the fusion of autophagosomes with lysosomes and enhance apoptosis induced by menadione via mitochondrial pathway. The results demonstrated generation and accumulation of reactive oxygen species and increased levels of ubiquitinated proteins and GRP78 in cells treated with both menadione and NH(4)Cl. Our data indicates that lysosomal system through autophagy plays an important role in preventing menadione-induced apoptosis in Hela cells by clearing misfolded proteins, which alleviates endoplasmic reticulum stress.
authors.affiliation: Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Yu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Huang
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Jiateng
authors.initials: J
authors.lastname: Zhong
authors.forename: Jinsong
authors.initials: J
authors.lastname: Kang
authors.forename: Yuhe
authors.initials: Y
authors.lastname: Liu
authors.forename: Liankun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D005260:Female; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000378:metabolism*; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D017382:Reactive Oxygen Species; D057149:Ubiquitinated Proteins; D000643:Ammonium Chloride; D024483:Vitamin K 3