58-F, a flavanone from Ophiopogon japonicus, prevents hepatocyte death by decreasing lysosomal membrane permeability.
Lysosome membrane permeabilization (LMP) has been implicated in cell death. In the present study, we investigated the relationship between cell death and H2O2-/CCl4-induced LMP in hepatocytes in vitro and following acute liver injury in vivo. The key finding was that H2O2 triggered LMP by oxidative stress, as evidenced by a suppression of LAMP1 expression, a reduction in LysoTracker Green and AO staining, and the leakage of proton and cathepsin B/D from the lysosome to the cytoplasm, resulting in cell death. CCl4 also triggered hepatocyte death by decreasing lysosome LAMP1 expression and by inducing the accumulation of products of peroxidative lipids and oxidized proteins. Furthermore, a novel compound 5,8-dimethoxy-6-methyl-7-hydroxy-3-3(2-hydroxy-4-methoxybenzyl) chroman-4-one (58-F) was extracted from Ophiopogon japonicus and served as a potential therapeutic drug. In vivo and in vitro results showed that 58-F effectively rescued hepatocytes by decreasing LMP and by inducing lysosomal enzyme translocation to the cytosol.
Department of Biology, school of basic medical science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Xiaofeng
X
Yan
Department of Biology, school of basic medical science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Tingjie
T
Ye
Department of Biology, school of basic medical science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Xudong
X
Hu
Department of Biology, school of basic medical science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Pei
P
Zhao
Department of Biology, school of basic medical science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Xiaoling
X
Wang
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D047309:Flavones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D022781:Hepatocytes; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007425:Intracellular Membranes / Q000378:metabolism* / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D031441:Ophiopogon / Q000737:chemistry*; D010539:Permeability / Q000187:drug effects
D047309:Flavones; D006861:Hydrogen Peroxide; C043562:flavone