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山东大学学报 (医学版) ›› 2017, Vol. 55 ›› Issue (12): 1-6.doi: 10.6040/j.issn.1671-7554.0.2016.1702

• 基础医学 •    下一篇

EGCG抑制内质网应激减轻高糖致HK-2细胞凋亡的作用

项春红1,吕丽2*,江蓓1,肖晓燕1,胡昭1   

  1. 1.山东大学齐鲁医院肾内科, 山东 济南 250012;2.内蒙古科技大学包头医学院第一附属医院肾内科, 内蒙古 包头 014010
  • 出版日期:2017-12-20 发布日期:2022-09-27
  • 通讯作者: 胡昭. E-mail:sdhuzhao@163.com*共同第一作者.
  • 基金资助:
    中国博士后科学基金面上项目(2015M572048);齐鲁医院临床研究项目(2014QLKY13)

Mechanism of EGCG protecting high-glucose-induced HK-2 cell apoptosis by suppressing endoplasmic reticulum stress

XIANG Chunhong1, LÜ Li2*, JIANG Bei1, XIAO Xiaoyan1, HU Zhao1   

  1. 1. Department of Nephrology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. Department of Nephrology, First Affiliated Hospital of Baotou Medical College of Inner Mongolia, Baotou 014010, Inner Mongolia, China
  • Online:2017-12-20 Published:2022-09-27

摘要: 目的 探究表没食子儿茶素没食子酸酯(EGCG)对高糖环境下人肾小管上皮细胞(HK-2)的保护作用。 方法 根据高糖可诱导HK-2细胞损伤将细胞分为正常糖组、甘露醇组、高糖组及不同浓度的EGCG组,干预HK-2细胞24 h后,采用CCK8法检测HK-2细胞的增殖。Hoechst33258染色和Annexin V法检测正常糖组、甘露醇组、高糖组、(20 μmol/L)EGCG组作用24 h后HK-2细胞凋亡;Western blotting检测上述4组HK-2细胞内质网应激反应蛋白GRP78和Caspase-12蛋白的表达。 结果 高糖组培养HK-2 细胞24 h后,细胞增殖较正常糖组明显降低,细胞凋亡较正常糖组明显增加(P<0.001)。(20 μmol/L)EGCG组干预24 h后能明显改善高糖环境下HK-2细胞的增殖。EGCG(20 μmol/L)作用24 h后能明显降低细胞的凋亡率(P<0.001),且EGCG干预后内质网应激反应蛋白GRP78和Caspase-12蛋白表达较高糖组也明显降低(P=0.001)。 结论 EGCG可能通过抑制内质网应激介导的凋亡途径改善高糖致HK-2细胞的凋亡。

关键词: 表没食子儿茶素没食子酸酯, 内质网应激, 人肾小管上皮细胞, 细胞凋亡

Abstract: Objective To investigate the protective effect and mechanism of epigallocatechin 3-gallate(EGCG)on HK-2 cells exposed to high glucose. Methods The HK-2 cells were divided into normal glucose group, mannitol group, high glucose group, and EGCG group. After 24-hour treatment, cell proliferation was measured with CCK8; cell apoptosis was measured with Hoechst33258 and Annexin V staining; the expressions of GRP78 and Caspase-12 were determined with Western blotting. Results Compared with the normal glucose group, the high glucose group showed significantly inhibited cell proliferation and increased apoptosis(P<0.001), while the EGCG(20 μmol/L)group displayed significantly improved cell proliferation, reduced apoptosis rate(P<0.001), and decreased GRP78 and Caspase-12 expressions(P=0.001). Conclusion EGCG may reduce high-glucose-induced HK-2 apoptosis by inhibiting endoplasmic reticulum stress.

Key words: Epigallocatechin 3-gallate, Endoplasmic reticulum stress, HK-2 cells, Apoptosis

中图分类号: 

  • R692.6
[1] Vallon V, Thomson SC. Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney[J]. Annu Rev Physiol, 2012, 74: 351-375. doi: 10.1146/annurev-physiol-020911-153333.
[2] Zhu YJ, Cui HW, Xia YF, et al. RIPK3-mediated necroptosis and apoptosis contributes to renal tubular cell progressive loss and chronic kidney disease progression in rats[J]. PLoS One, 2016, 6(11): e0156729.
[3] Roberto B, Valentina P, Damian G, et al. Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration[J]. Int Rev Cell Mol Biol, 2013, 301: 215-290. doi: 10.1016/B978-0-12-407704-1.00005-1.
[4] Nakagawa T, Zhu H, Morishima N, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta[J]. Nature, 2000, 6765(403): 98-103.
[5] Granja A, Pinheiro M, Reis S. Epigallocatechin gallate nanodelivery systems for cancer therapy[J]. Nutrients, 2016, 5(8). doi:10.3390/nu8050307.
[6] Garnet JL, Nicolas G, Hasna M, et al. Bcl-2-modifying factor induces renal proximal tubular cell apoptosis in diabetic mice[J]. Diabetes, 2012, 2(61): 474-484.
[7] 吴蔚桦. 细胞程序性死亡与糖尿病肾病发病机制研究进展[J/CD].中华肾病研究, 2015, 4(4): 212-214. WU Weihua. Progress of research on the role of programmed cell death in the pathogenesis of diabetic nephropathy[J/CD]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2015, 4(4): 212-214.
[8] Moritz RJ, LeBaron RG, Phelix CF, et al. Macrophage TGF-β1 and the proapoptotic extracellular matrix protein BIGH3 induce renal cell apoptosis in prediabetic and diabetic conditions[J]. Int J Clin Med, 2016, 7(7): 496-510.
[9] 王娜娜, 李雪峰, 王淑君, 等. 不同病理类型肾综患者尿蛋白对肾小管上皮细胞增殖和凋亡相关蛋白FAS表达的影响[J]. 中国中西医结合肾病杂志, 2013, 14(11): 955-958. WANG Nana, LI Xuefeng, WANG Shujun, et al. Effects of different quality proteinuria on proliferation and apoptosis in human renal tubular epithelial cells[J]. Chinese Journal of Integrated Traditional and Western Nephrology, 2013, 14(11): 955-958.
[10] Kelly DJ, Stein-Oakley A, Zhang Y, et al. Fas-induced apoptosis is a feature of progressive diabetic nephropathy in transgenic(mRen-2)27 rats: attenuation with renin-angiotensin blockade[J]. Nephrology(Carlton), 2004, 1(9): 7-13.
[11] Sun XY, Qin HJ, Zhang Z, et al. Valproate attenuates diabetic nephropathy through inhibition of endoplasmic reticulum stress-induced apoptosis[J]. Mol Med Rep, 2016, 13(1): 661-668.
[12] Fan Y, Xiao WZ, Li ZZ, et al. Erratum: RTN1 mediates progression of kidney disease by inducing ER stress[J]. Nat Commun, 2015, 6: 8710. doi:10.1038/ncomms9710.
[13] Fu XL, Gao DS. Endoplasmic reticulum proteins quality control and the unfolded protein response: the regulative mechanism of organisms against stress injuries[J]. Biofactors, 2014, 6(40): 569-585.
[14] Kong F, Han F, Xu Y, et al. Molecular mechanisms of IRE1α-ASK1 pathway reactions to unfolded protein response in DRN neurons of post-traumatic stress disorder rats[J]. J Mol Neurosci, 2017, 4(61): 531-541.
[15] McGuckin MA, Eri RD, Das I, et al. ER stress and the unfolded protein response in intestinal inflammation[J]. Am J Physiol Gastrointest Liver Physiol, 2010, 6(298): 820-832.
[16] Xiong Y, Chen H, Lin P, et al. ATF6 knock-down decreases apoptosis, arrests the S phase of the cell cycle and increases steroid hormone production in mouse granulosa cells[J]. Am J Physiol Cell Physiol, 2017, 312(3): 341-353.
[17] Feng D, Wang B, Wang L, et al. Pre-ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting ER stress-dependent autophagy via PERK and IRE1 signalings[J]. J Pineal Res, 2017, 62(3). doi: 10.1111/jpi.12395. Epub 2017 Mar 6.
[18] Wang G, Yang ZQ, Zhang K. Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential[J]. Am J Transl Res, 2010, 1(2): 65-74.
[19] Cao YP, Hao YM, Li H, et al. Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose[J]. Int J Mol Med, 2014, 4(33): 809-816.
[20] Zhu W, Xu Jing, Ge YY, et al. Epigallocatechin-3-gallate(EGCG)protects skin cells from ionizing radiation via heme oxygenase-1(HO-1)overexpression[J]. J Radiat Res, 2014, 55(6): 1056-1065.
[21] Michelle AK, Huei LHN, Dino P, et al. Vascular and Metabolic Actions of the Green Tea Polyphenol Epigallocatechin Gallate[J]. Curr Med Chem, 2015, 22(1): 59-69.
[22] Seyedeh SS, Mehran SH, Ali S, et al. Epigallocatechin gallate/layered double hydroxide nanohybrids: preparation, characterization, and in vitro anti-tumor study[J]. PLoS One, 2015, 8(10): e0136530.
[23] Gao Z, Han Y, Hu Y, et al. Targeting HO-1 by epigallocatechin-3-gallate reduces contrast-induced renal injury via anti-oxidative stress and anti-inflammation pathways[J]. PLoS one, 2016, 2(11): e0149032.
[24] 代春美, 宋玉泽, 杨伟, 等. EGCG 对高糖诱导的HK-2细胞氧化应激损伤的保护作用[J]. 天然产物研究与开发, 2016, 5(28): 673-679. DAI Chunmei, SONG Yuze, YANG Wei, et al. EGCG protects HK-2 cells damage induced by high glucose against oxidative stress[J]. Nat Prod Res Dev, 2016, 5(28): 673-679.
[25] Chen BB, Liu GY, Zou PM, et al. Epigallocatechin-3-gallate protects against cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis[J]. Exp Biol Med(Maywood), 2015, 11(240): 1513-1519.
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