Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition.
Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition.
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糖尿病条件下，锌对于体外人肾小管细胞和体内小鼠肾中 Nrf2 的转录功能至关重要
DOI：
10.1111/jcmm.12239
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发表时间：
2014-05
影响因子：
5.3
通讯作者：
Cai L
中科院分区：
文献类型：
--
作者：
Li B;Cui W;Tan Y;Luo P;Chen Q;Zhang C;Qu W;Miao L;Cai L
越来越多的人体和实验室研究表明锌对糖尿病并发症的影响。核因子-红细胞2相关因子2（Nrf2）在抗氧化损伤中起重要作用。本研究旨在探讨缺锌或补锌对高糖（HG）诱导的人肾小管上皮细胞（HK 11）Nrf2表达和功能的影响，以及对高糖（HG）诱导的糖尿病小鼠肾脏损伤程度的影响。对于锌缺乏糖尿病小鼠，每天用锌螯合剂PTEN以5mg/kg bw治疗4个月。结果显示，HG/TPEN可显著增加HK11细胞中促纤维化介质结缔组织生长因子（CTGF）和PAI-1的表达，而TPEN可使HK11细胞内游离锌耗竭，Nrf2表达和转录降低，从而加重了HG/TPEN的促纤维化作用。补充锌可阻止TPEN的作用，并增加Akt和GSK-3 β磷酸化，同时减少Nrf2核输出蛋白Fyn。Akt抑制剂可阻断Zn的上述作用。因此，Zn通过激活Akt介导的Fyn功能抑制来上调Nrf2功能。用TPEN治疗糖尿病小鼠降低肾脏Zn水平和Nrf2表达和转录，并加重肾脏氧化损伤、炎症和纤维化。这些结果表明锌对Nrf2表达和转录功能的重要性。
Increasing evidence from human and laboratory studies showed the effect of zinc (Zn) on diabetic complications. Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays important role in the prevention of oxidative damage. This study was to define whether Zn statues (deficiency or supplement) affect the Nrf2 expression and function, and also affect the damage severity of human renal tubular (HK11) cells exposed to high glucose (HG) with palmitate (Pal) and kidney of diabetic mice induced by multiple low-dose streptozotocins. For Zn deficiency diabetic mice were treated with Zn chelator PTEN at 5 mg/kg bw daily for 4 months. Results showed that HG/Pal significantly increased the expression of pro-fibrotic mediators, connective tissue growth factor and PAI-1, in HK11 cells, which was exacerbated by TPEN that depleted intracellular free Zn and decreased Nrf2 expression and transcription. Zn supplement prevented the effects of TPEN and also increased Akt and GSK-3β phosphorylation with a decrease in Nrf2 nuclear exporter, Fyn. All these effects of Zn were abolished by Akt inhibitor. Therefore, Zn up-regulates Nrf2 function via activating Akt-mediated inhibition of Fyn function. Treatment of diabetic mice with TPEN decreased renal Zn level and Nrf2 expression and transcription, with an exacerbation of renal oxidative damage, inflammation and fibrosis. These results suggest the essentiality of Zn for Nrf2 expression and transcription function.
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影响因子：
4.4
作者：
Ha, Khoi-Nguyen;Chen, Yan;Sternberg, Paul, Jr.
通讯作者：
Sternberg, Paul, Jr.
内皮素-1介导的金属硫蛋白和痕量金属的变化在慢性糖尿病大鼠的肝脏和肾脏中。
DOI：
10.1080/15604280214281
发表时间：
2002-07
期刊：
International journal of experimental diabetes research
影响因子：
--
作者：
Cai, Lu;Chen, Shali;Evans, Terry;Cherian, M George;Chakrabarti, Subrata
通讯作者：
Chakrabarti, Subrata
影响因子：
3.5
作者：
Brandao-Neto, J;Silva, CAB;Diniz, JMM
通讯作者：
Diniz, JMM
影响因子：
4.8
作者：
Jayawardena R;Ranasinghe P;Galappatthy P;Malkanthi R;Constantine G;Katulanda P
通讯作者：
Katulanda P
影响因子：
4.2
作者：
Hambidge, K. Michael;Krebs, Nancy F.
通讯作者：
Krebs, Nancy F.