Expression and clinical significance of GRP78 in human trabecular meshwork cells
CHAI Fang1 ZHUO Yehong2 YANG Xinguang1▲
1.Department of Ophthalmology, Xi'an No.4 Hospital Ophthalmic Medical Center of Shaanxi Province Guangren Hospital Affiliated to School of Medicine, Xi'an Jiaotong University, Shaanxi Province, Xi'an 710004, China; 2.Zhongshan Ophthalmic Center, Sun Yat-Sen University State Key Laboratory of Ophthalmology, Guangdong Province, Guangzhou 510060, China
Abstract：[Abstract] Objective To detect protein and mRNA expression differences of GRP78 in human trabecular meshwork cells of normal eyes (NTM) and POAG patients (GTM) in vitro. Methods Human trabecular meshwork cells from NTM and GTM in vitro were divided into 3 groups: Tunicamycin (Tm) group, Staurosporine (STS) group and control group. Real-time RT-PCR and Western blot were used to detect the expression of mRNA and protein of GRP78 in trabecular meshwork cells after 6, 24 h treatment. Results The expression of GRP78 in primary culture GTM cells was significantly lower than that in NTM cells, with statistically significant difference (P < 0.05). Tm could increase the expression of GRP78 in NTM and GTM cells, the expression in GTM cells was lower than that in NTM cells, with statistically significant difference (P < 0.05). The response of GTM cells for STS was bigger than NTM cells. Conclusion GTMs showed insensitivity reactions when stimulated with inducer of endoplasmic reticulum stress, reduce the expression of GRP78, lead to the increased sensitivity of GTMs to damage stimulus. GRP78 may play a cytoprotective role in the apoptosis in trabecular meshwork cells caused by endoplasmic reticulum stress.
[参考文献]
[1] Quigley HA，Broman AT. The number of people with glaucoma worldwide in 2010 and 2020 [J]. Br J Ophthalmol，2006，90（3）：262-267.
[2] 葛坚.我国近五年青光眼临床和基础研究进展[J].中华眼科杂志，2005，41（8）：710-715.
[3] Sano R，Reed JC. ER stress-induced cell death mechanisms [J]. Biochim Biophys Acta，2013，1833（12）：3460-3470.
[4] 林明楷，葛坚，卓业鸿，等.青光眼病人小梁细胞体外培养、冻存与复苏[J].中国实用眼科杂志，2000，18（2）：77-79.
[5] Ozasa R，Okada T，Nadanaka S，et al. The antipsychotic olanzapine induces apoptosis in insulin-secreting pancreatic β cells by blocking PERK-mediated translational attenuation [J]. Cell Struct Funct，2013，38（2）：183-195.
[6] Joel M，Lisa C，Anna N. Stress and the inflammatory process：a major cause of pancreatic cell death in type 2 diabetes [J]. Diabetes Metab Syndr Obes，2014，7：25-34.
[7] Zhou Y，Shu F，Liang X，et al. Ampelopsin Induces Cell Growth Inhibition and Apoptosis in Breast Cancer Cells through ROS Generation and Endoplasmic Reticulum Stress Pathway [J]. PLoS One，2014，9（2）：e89021.
[8] Suyama K，Watanabe M，Sakabe K，et al. GRP78 suppresses lipid peroxidation and promotes cellular antioxidant levels in glial cells following hydrogen peroxide exposure [J]. PLoS One，2014，9（1）：e86951.
[9] Osada N，Kosuge Y，Ishige K. Characterization of neuronal and astroglial responses to ER sress in the hippocampal CAI area in mice following transient forebrain ischemia [J]. Neurochem Int，2010，57（1）：1-7.
[10] 安琳，季健.原发性开角型青光眼房水外流通路改变的研究进展[J].中华眼科杂志，2011，47（10）：953-956.
[11] Luna C，Li G，Liton PB，et al. Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells [J]. Food Chem Toxicol，2009，47（1）：198-204.
[12] 张亚琴，徐亮，李建军，等.正常眼压性青光眼的研究现状[J].国际眼科纵览，2011，35（1）：9-13.
[13] Qian Y，Tiffany-Castiglioni E. Lead-induced endoplasmic reticulum（ER）stress responses in the nervous system [J]. Neurochem Res，2003，28（1）：153-162.
[14] 关丽英，许彩民，潘华珍.内质网应激介导的细胞凋亡[J].生物化学与生物物理进展，2007，34（11）：1136-1141.
[15] 钱锦，孙晓东.内质网应激与眼科疾病[J].眼科新进展，2007，11（27）：861-864.
[16] 王淑雅，华宁，李筱荣.PERK通路介导的内质网应激与眼科疾病研究进展[J].中华眼科杂志，2012，48（8）：759-762.
[17] Li G，Luna C，Qiu J，et al. Role of miR-204 in the regulation of apoptosis，endoplasmic reticulum stress response，and inflammation in human trabecular meshwork cells [J]. Invest Ophthalmol Vis Sci，2011，52（6）：2999-3007.
[18] Pi L，Li X，Song Q，et al. Knockdown of glucose-regulated protein 78 abrogates chemoresistance of hypopharyngeal carcinoma cells to cisplatin induced by unfolded protein in response to severe hypoxia [J]. Oncol Lett，2014，7（3）：685-692.
[19] 张欣，王玉明，段勇.GRP78研究新进展[J].现代检验医学杂志，2014，（6）：5-8.
[20] 韩真，王大博.葡萄糖调节蛋白在急性高眼压大鼠视网膜中的表达及其意义[J].眼科研究，2012，30（5）：424-427.
京公网安备 11010502046598号