Zinc deficiency induces oxidative stress and AP-1 activation in 3T3 cells
Zinc deficiency induces oxidative stress and AP-1 activation in 3T3 cells
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DOI：
10.1016/s0891-5849(00)00200-8
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发表时间：
2000-04-01
影响因子：
7.4
通讯作者：
Keen, CL
中科院分区：
文献类型：
--
作者：
Oteiza, PI;Clegg, MS;Keen, CL
据推测，缺锌引起的组织改变的机制之一是过度的细胞氧化损伤。在本研究中，我们研究了锌缺乏是否会诱导 3T3 细胞的氧化应激，并触发与氧化应激相关的特定细胞内反应。将细胞暴露于对照培养基或含有0.5、5或50μM锌的螯合培养基24或48小时。通过探针 5(或 6)-羧基-2'7'-二氯二氢荧光素二乙酸酯 (DCDCDHF) 荧光的增加来评估细胞的氧化状态。暴露24和48小时后，0.5和5μM Zn组的荧光强度明显高于50μM Zn和对照组（4至15倍）。与 50 μM Zn 组和对照组相比，0.5 和 5 μM Zn 细胞中抗氧化酶 CuZn (CuZnSOD) 和 Mn (MnSOD) 超氧化物歧化酶的活性在 24 小时和 48 小时时间点均显着较高。这些较高的活性与较高水平的 MnSOD mRNA 相关。培养24小时后，0.5和5μM Zn细胞中活化的AP-1水平明显高于对照（分别为72%和58%）和50 I-LM Zn细胞（分别为73%和60%）。 0.5 和 5 muM Zn 细胞中的 NF-κ B 结合活性低于对照。因此，氧化应激是由 3T3 细胞缺锌引起的。这种氧化应激导致氧化防御机制上调。 (C) 2000 爱思唯尔科学公司。
It has been postulated that one mechanism underlying zinc deficiency-induced tissue alterations is excessive cellular oxidative damage. In the present study we investigated if zinc deficiency can induce oxidative stress in 3T3 cells and trigger select intracellular responses that have been associated to oxidative stress. Cells were exposed to control media or to chelated media containing 0.5, 5, or 50 mu M zinc for 24 or 48 h. The oxidative status of the cells was evaluated as an increase in the fluorescence of the probe 5(or 6)-carboxy-2'7'-dichlorodihydrofluorescein diacetate (DCDCDHF). After 24 and 48 h of exposure, the fluorescence intensity was significantly higher (4- to 15-fold) in the 0.5 and 5 mu M Zn groups compared to the 50 mu M Zn and control groups. The activity of the antioxidant enzymes CuZn (CuZnSOD) and Mn (MnSOD) superoxide dismutases was significantly higher in the 0.5 and 5 mu M Zn cells compared to the 50 mu M Zn and control groups at both the 24 and 48 h time points. These higher activities were associated with higher levels of MnSOD mRNA. After 24 h in culture, the level of activated AP-1 was markedly higher in the 0.5 and 5 mu M Zn cells than in the control (72 and 58%, respectively) and 50 I-LM Zn cells (73 and 60%, respectively). NF-kappa B binding activity was lower in the 0.5 and 5 mu M Zn cells than in controls. Thus, oxidative stress is induced by zinc deficiency in 3T3 cells. This oxidative stress results in an upregulation of oxidant defense mechanisms. (C) 2000 Elsevier Science Inc.