Graduate School of Environmental Science, Hokkaido University, Sapporo, 060-0810, Japan.
Faculty of Environmental Earth Science, Hokkaido University, Sapporo, 060-0810, Japan.
Biol Trace Elem Res. 2020 Dec;198(2):627-635. doi: 10.1007/s12011-020-02097-9. Epub 2020 Mar 3.
Exposure to cadmium (Cd) is a risk factor to health impairments, wherein its cytotoxicity is attributed to induction of oxidative stress. Usage of anti-oxidants, however, can help lessen the damaging effects of Cd. The effect of Cd interaction with low concentration of dietary anti-oxidants, L-ascorbic acid and (-)-epigallocatechin gallate (EGCG), to PC12 cellular mechanisms was examined. The expected toxicity of Cd was observed on PC12 cells but addition of L-ascorbic acid ameliorated this effect. On the other hand, addition of EGCG was able to increase the cytotoxicity of Cd and to decrease the protective effect of L-ascorbic acid against Cd. Increase in LDH activity and decrease in free sulfhydryl levels indicated cell membrane damage and oxidative stress, respectively, in Cd- and EGCG-Cd-treated cells. Downregulation of pro-apoptotic proteins (pro-caspase-9, p53, and ERK1) was observed in cells treated with Cd alone and EGCG-Cd, while upregulation of autophagy-linked proteins (p62 and pBeclin1) was found on L-ascorbic acid-Cd combination treatments. These findings indicate that Cd causes cells to undergo an autophagy-enhanced cell death; low-concentration EGCG and L-ascorbic acid promotes cell survival individually; however, interaction of EGCG with Cd showed enhancement of Cd toxicity and antagonism of L-ascorbic acid efficiency.
镉（Cd）暴露是对健康损害的一个风险因素，其细胞毒性归因于诱导氧化应激。然而，使用抗氧化剂可以帮助减轻 Cd 的破坏性影响。研究了 Cd 与低浓度膳食抗氧化剂 L-抗坏血酸和（-）-表没食子儿茶素没食子酸酯（EGCG）相互作用对 PC12 细胞机制的影响。观察到 Cd 对 PC12 细胞的预期毒性，但添加 L-抗坏血酸减轻了这种作用。另一方面，添加 EGCG 能够增加 Cd 的细胞毒性，并降低 L-抗坏血酸对 Cd 的保护作用。LDH 活性的增加和游离巯基水平的降低分别表明 Cd 和 EGCG-Cd 处理的细胞中细胞膜损伤和氧化应激。单独用 Cd 和 EGCG-Cd 处理的细胞中观察到促凋亡蛋白（procaspase-9、p53 和 ERK1）下调，而在 L-抗坏血酸-Cd 联合处理的细胞中观察到自噬相关蛋白（p62 和 pBeclin1）上调。这些发现表明，Cd 导致细胞发生自噬增强的细胞死亡；低浓度的 EGCG 和 L-抗坏血酸单独促进细胞存活；然而，EGCG 与 Cd 的相互作用显示出 Cd 毒性的增强和 L-抗坏血酸效率的拮抗作用。
