Zinc Modulates High Glucose-Induced Apoptosis by Suppressing Oxidative Stress in Renal Tubular Epithelial Cells
Zinc Modulates High Glucose-Induced Apoptosis by Suppressing Oxidative Stress in Renal Tubular Epithelial Cells
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锌通过抑制肾小管上皮细胞的氧化应激来调节高葡萄糖诱导的细胞凋亡
DOI：
10.1007/s12011-014-9922-x
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发表时间：
2014-03
影响因子：
3.9
通讯作者：
Chi, Zhi-Hong
中科院分区：
文献类型：
--
作者：
Chu, Qingqing;Wang, Zhan-You;Li, Hongjuan;Chi, Zhi-Hong
高血压是糖尿病肾病的特征，通过引发氧化应激和炎症诱导肾小管细胞凋亡。锌（Zn）被认为是许多酶和蛋白质中的必需微量元素，这些酶和蛋白质参与抗氧化防御、电子传递以及发挥抗凋亡或细胞保护作用。本研究采用体外培养的肾小管上皮细胞（NRK-52 E），探讨锌对高糖诱导的细胞毒性的保护作用及其机制。作者发现，锌补充抑制高糖（HG）诱导的NRK-52 E细胞凋亡，通过减少活性氧的产生，抑制HG诱导的caspase-3和caspase-9的激活，并抑制细胞色素c从线粒体释放到胞质溶胶。进一步的分析表明，锌补充促进细胞存活，通过增加核转位的NF-E2相关因子2（Nrf 2），导致增加的两种抗氧化酶，血红素加氧酶-1和谷氨酸半胱氨酸连接酶的水平的调节，这提供了一个适应性的生存反应，对汞诱导的氧化细胞毒性。此外，锌介导的Nrf 2活性的增加被Akt或细胞外信号调节激酶1/2的药理学抑制所抑制。综上所述，这些发现表明，锌通过激活Akt和ERK信号通路的抗凋亡能力导致Nrf 2激活，随后，Nrf 2靶基因诱导，从而保护NRK-52 E细胞免受HG诱导的凋亡。
Hyperglycemia is a characteristic of diabetic nephropathy, inducing renal tubular cell apoptosis by eliciting oxidative stress and inflammation. Zinc (Zn) is known as an essential trace element in many enzymes and proteins involved in antioxidant defenses, electron transport, and exerting antiapoptotic or cytoprotective effects. In this study, the underlying mechanisms involved in the protective effects of Zn on high glucose-induced cytotoxicity were explored using cultured renal tubular epithelial cells (NRK-52E). The authors discovered that Zn supplementation inhibited high glucose (HG)-induced NRK-52E cell apoptosis by attenuating reactive oxygen species production, inhibiting HG-induced caspase-3 and caspase-9 activation, and inhibiting the release of cytochrome c from mitochondria to the cytosol. Further analysis revealed that Zn supplementation facilitated cell survival through increasing nuclear translocation of NF-E2-related factor 2 (Nrf2), leading to increased regulation of levels of two antioxidant enzymes, hemeoxygenase-1 and glutamate cysteine ligase, which provided an adaptive survival response against the HG-induced oxidative cytotoxicity. Moreover, the Zn-mediated increases in Nrf2 activity were suppressed by the pharmacological inhibition of Akt or extracellular signal-regulated kinase 1/2. Taken together, these findings suggest that Zn antiapoptosis capacity through the activation of Akt and ERK signal pathways leads to Nrf2 activation and, subsequently, Nrf2 target gene induction, thereby protecting the NRK-52E cells from HG-induced apoptosis.
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影响因子：
3
作者：
T. Nishiura;K. Abe
通讯作者：
T. Nishiura;K. Abe
DOI：
--
发表时间：
2009
期刊：
--
影响因子：
--
作者：
Limei Liu;T. Zheng;Feng Wang;Niansong Wang;Yanyan Song;Ming Li;Lifang Li;Jiamei Jiang;Weijing Zhao
通讯作者：
Limei Liu;T. Zheng;Feng Wang;Niansong Wang;Yanyan Song;Ming Li;Lifang Li;Jiamei Jiang;Weijing Zhao
影响因子：
19.6
作者：
Verzola, D.;Gandolfo, M. T.;Garibotto, G.
通讯作者：
Garibotto, G.
影响因子：
7.8
作者：
Bao, Bin;Prasad, Ananda S.;Swerdlow, Paul
通讯作者：
Swerdlow, Paul
影响因子：
3
作者：
Nishiura, Toshihiro;Abe, Kimio
通讯作者：
Abe, Kimio