58-F, a flavanone from Ophiopogon japonicus, prevents hepatocyte death by decreasing lysosomal membrane permeability.
58-F, a flavanone from Ophiopogon japonicus, prevents hepatocyte death by decreasing lysosomal membrane permeability.
复制标题
58-F 是一种来自麦冬的黄烷酮，通过降低溶酶体膜通透性来防止肝细胞死亡
DOI：
10.1038/srep27875
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发表时间：
2016-06-16
影响因子：
4.6
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Yan X;Ye T;Hu X;Zhao P;Wang X
溶酶体膜透化（LMP）与细胞死亡有关。在本研究中，我们研究了细胞死亡和H2 O2-/CCl 4-诱导的LMP在体外肝细胞和急性肝损伤在体内之间的关系。关键发现是H2 O2通过氧化应激触发LMP，如通过抑制LAMP 1表达、LysoTracker绿色和AO染色减少以及质子和组织蛋白酶B/D从溶酶体泄漏到细胞质中所证明的，导致细胞死亡。CCl 4还通过降低溶酶体LAMP 1表达和诱导过氧化脂质和氧化蛋白产物的积累来触发肝细胞死亡。此外，从麦冬中提取得到一个新化合物5，8-二甲氧基-6-甲基-7-羟基-3-3-（2-羟基-4-甲氧基苄基）色满-4-酮（58-F），该化合物具有潜在的治疗作用。体内和体外结果表明，58-F通过降低LMP和诱导溶酶体酶易位到胞质溶胶来有效地拯救肝细胞。
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.