Role of Zinc in the Regulation of Autophagy During Ethanol Exposure in Human Hepatoma Cells
Role of Zinc in the Regulation of Autophagy During Ethanol Exposure in Human Hepatoma Cells
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DOI：
10.1007/s12011-013-9816-3
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发表时间：
2013-12-01
影响因子：
3.9
通讯作者：
Yoo, Chanwong
中科院分区：
文献类型：
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作者：
Liuzzi, J. P.;Yoo, Chanwong
自噬与多种疾病有关，包括神经退行性疾病、糖尿病和癌症。越来越多的证据支持这样的观点，即自噬的激活可以防止乙醇诱导的脂肪变性和肝损伤。在此，我们研究了锌在暴露或不暴露于乙醇的人肝癌细胞VL-17 A中自噬的作用。LC 3 II/LC 3 I比率、p62和Beclin-1表达和自噬体数目在含有不同浓度锌的培养基中孵育的细胞中测定，所述锌有或没有乙醇。此外，在暴露于乙醇和自噬抑制剂3-甲基腺嘌呤的细胞中评估了不稳定的锌和金属硫蛋白和锌转运蛋白SLC 39 A8、SLC 39 A14和SLC 30 A10的mRNA表达。锌耗竭引起细胞自噬的显著抑制。相反，锌除了培养基刺激细胞中的自噬。此外，与乙醇和过量锌（40 μ M）的共治疗有一个加性的自噬诱导的效果。3-甲基腺嘌呤处理降低了不稳定的锌，但这种效果在暴露于乙醇的细胞中更为明显。最后，乙醇和3-甲基腺嘌呤引起金属硫蛋白和锌转运蛋白表达的显着变化。这项研究的结果支持了锌在基础条件下和乙醇暴露期间对自噬至关重要的假设。
Faulty autophagy has been linked to various diseases including neurodegenerative disorders, diabetes, and cancer. Increasing evidence support the notion that activation of autophagy protects against ethanol-induced steatosis and liver injury. Herein, we investigated the role of zinc in autophagy in human hepatoma cells VL-17A exposed or not to ethanol. LC3II/LC3I ratio, p62, and Beclin-1 expression and autophagosomes number were determined in cells incubated in medium containing various concentrations of zinc with or without ethanol. In addition, labile zinc and mRNA expression of metallothionein and the zinc transporters SLC39A8, SLC39A14, and SLC30A10 were evaluated in cells exposed to ethanol and the autophagy inhibitor 3-methyladenine. Zinc depletion caused a significant suppression of autophagy in cells. Conversely, zinc addition to medium stimulated autophagy in cells. Moreover, cotreatment with ethanol and excess zinc (40 mu M) had an additive effect on the induction of autophagy. 3-methyadenine treatment decreased labile zinc, but this effect was more pronounced in cells exposed to ethanol. Lastly, ethanol and 3-methyladenine caused significant changes in the expression of metallothionein and zinc transporters. The results from this study support the hypothesis that zinc is critical for autophagy under basal conditions and during ethanol exposure.