Department of Nephrology, Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province 518000, PR China; Department of Pathophysiology, China Medical University, Shenyang, Liaoning Province 110001, PR China.
Department of Pathophysiology, China Medical University, Shenyang, Liaoning Province 110001, PR China.
Diabetes Res Clin Pract. 2021 Feb;172:108445. doi: 10.1016/j.diabres.2020.108445. Epub 2020 Sep 17.
Apoptosis and oxidant stress are known to be involved in the pathogenesis of diabetic kidney disease (DKD). We have previously reported that zinc transporter 7 in SLC30 family (SLC30A7) inhibits apoptosis in rat peritoneal mesothelial cells under high glucose (HG) conditions. In the current study, we aimed to investigate whether SLC30A7 had effect for anti-oxidant stress in renal tubular epithelial cells under HG.
SLC30A7 in HG-induced apoptosis in a normal rat kidney tubular epithelial cell line (NRK-52E cells)/kidneys of STZ-induced diabetic mice was examined and the activity of nuclear factor erythroid 2-related factor 2 (NFE2L2) was further analyzed by using real time RT-PCR, siRNA and Western blot protocols.
SLC30A7 was found to be up-regulated, while NFE2L2 was activated in kidneys of STZ-induced diabetic mice and HG-induced apoptosis of NRK-52E cells. Knock-down of SLC30A7 with siRNA protocol resulted in lower intracellular free zinc levels in the cells and decreased zinc distribution in the Golgi apparatus. Furthermore, knock-down of NFE2L2 down-regulated its target HMOX1 gene expression, decreased SLC30A7 activity but increased HG-induced apoptosis.
The current study provides new evidence that SLC30A7 has anti-oxidant stress effects in HG-induced apoptosis via the NFE2L2/HMOX1 signal transduction pathway.
细胞凋亡和氧化应激被认为与糖尿病肾病（DKD）的发病机制有关。我们之前的研究表明，SLC30 家族中的锌转运体 7（SLC30A7）可抑制高糖（HG）条件下大鼠腹膜间皮细胞的凋亡。在本研究中，我们旨在研究 SLC30A7 在 HG 条件下对肾小管上皮细胞的抗氧化应激是否有作用。
采用实时 RT-PCR、siRNA 和 Western blot 方案检测 HG 诱导的正常大鼠肾小管上皮细胞系（NRK-52E 细胞）/链脲佐菌素诱导的糖尿病小鼠肾脏中 SLC30A7 诱导的细胞凋亡，进一步分析核因子红细胞 2 相关因子 2（NFE2L2）的活性。
在 STZ 诱导的糖尿病小鼠肾脏和 HG 诱导的 NRK-52E 细胞凋亡中发现 SLC30A7 上调，而 NFE2L2 被激活。用 siRNA 方案敲低 SLC30A7 会导致细胞内游离锌水平降低，高尔基体内锌分布减少。此外，敲低 NFE2L2 下调其靶基因 HMOX1 的表达，降低 SLC30A7 的活性，但增加 HG 诱导的细胞凋亡。
本研究提供了新的证据，表明 SLC30A7 通过 NFE2L2/HMOX1 信号转导通路在 HG 诱导的细胞凋亡中具有抗氧化应激作用。
