Analysis of Cadmium, Epigallocatechin Gallate, and Vitamin C Co-exposure on PC12 Cellular Mechanisms
Analysis of Cadmium, Epigallocatechin Gallate, and Vitamin C Co-exposure on PC12 Cellular Mechanisms
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DOI：
10.1007/s12011-020-02097-9
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发表时间：
2020-03-03
影响因子：
3.9
通讯作者：
Kurasaki, Masaaki
中科院分区：
文献类型：
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作者：
Bondad, Serene Ezra C.;Kurasaki, Masaaki
镉（Cd）暴露是健康损害的危险因素，其中其细胞毒性归因于氧化应激的诱导。然而，使用抗氧化剂可以帮助减轻镉的破坏性影响。研究了镉与低浓度抗氧化剂L-抗坏血酸和表没食子儿茶素没食子酸酯（EGCG）交互作用对PC 12细胞机制的影响。镉对PC 12细胞有预期的毒性，但加入抗坏血酸可改善这种效应。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表明细胞膜损伤和氧化应激，分别在镉和EGCG-Cd处理的细胞。在单独镉和EGCG-Cd处理的细胞中观察到促凋亡蛋白（caspase-9，p53和ERK 1）的下调，而自噬相关蛋白（p62和pBeclin 1）的上调被发现在l-抗坏血酸-镉联合治疗。这些研究结果表明，镉导致细胞进行自噬增强的细胞死亡;低浓度的EGCG和l-抗坏血酸促进细胞存活单独的，然而，EGCG与镉的相互作用表现出增强的镉毒性和拮抗的l-抗坏血酸的效率。
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.