MicroRNA-124 Prevents H2O2 Induced Apoptosis and Oxidative Stress in Human Lens Epithelial Cells via Inhibition of the NF-κB Signaling Pathway

被引:28
作者
Gu, Xiu-li [1 ]
机构
[1] Yantaishan Hosp, Dept Ophthalmol, 91 Jiefang Rd, Yantai 264000, Shandong, Peoples R China
关键词
MicroRNA-124; NF-kappa B; Human lens epithelial cells; Apoptosis; Oxidative stress; NUCLEAR-FACTOR; IN-VITRO; EXPRESSION; MIR-124; CATARACT; AGE; ACTIVATION; GENE; PATHOGENESIS; DYSFUNCTION;
D O I
10.1159/000491433
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aim: To investigate the regulation of microRNA-124 (miRNA-124) on NF-kappa B pathway from H2O2-induced apoptosis and oxidative stress in human lens epithelial cells (hLEC). Methods: The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide) assay was used to detect hLEC viability. HLECs were divided into Blank, H2O2, mimics (miRNA-124 mimics) + H2O2, NC+ H2O2, pyrrolidine dithiocarbamate (PDTC; NF-kappa B signaling pathway inhibitor) + H2O2, and inhibitors (miRNA-124 inhibitors) + PDTC + H2O2 groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, Dichloro-dihydro-fluorescein diacetate to measure reactive oxygen species (ROS) production, and AnnexinV-FITC/PI staining to determine cell apoptosis. The mitochondrial membrane potential (MMP) was detected by fluorescence probe JC-1. Results: The H2O2-induced hLEC showed reductions in cell viability with decreased miRNA-124 but increased p-p65 in a dose-/time-dependent manner. Furthermore, ROS production, malondialdehyde content, Bax and Caspase-3 expressions, and cell apoptosis were elevated in H2O2-induced hLEC, whereas the activities of superoxide dismutase and glutathione peroxidase, Bcl-2 expression, MMP, as well as the mitochondrial energy metabolism genes were reduced. Additionally, miRNA-1 24 mimics and PDTC both decreased the p-p65 and reversed the cytotoxicity in H2O2-induced hLEC. Conclusion: MiRNA-124 prevents H2O2-induced oxidative stress and apoptosis in hLEC through suppressing the activation of the NF-kappa B pathway. (C) 2018 S. Karger AG, Basel
引用
收藏
页码:213 / 222
页数:10
相关论文
共 45 条
[1]   The Bcl-2 protein family: Arbiters of cell survival [J].
Adams, JM ;
Cory, S .
SCIENCE, 1998, 281 (5381) :1322-1326
[2]   Blindness and visual impairment due to age-related cataract in sub-Saharan Africa: a systematic review of recent population-based studies [J].
Bastawrous, Andrew ;
Dean, William H. ;
Sherwin, Justin C. .
BRITISH JOURNAL OF OPHTHALMOLOGY, 2013, 97 (10) :1237-1243
[3]   Evidence of oxidative stress in human corneal diseases [J].
Buddi, R ;
Lin, B ;
Atilano, SR ;
Zorapapel, NC ;
Kenney, MC ;
Brown, DJ .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2002, 50 (03) :341-351
[4]   Docosahexaenoic Acid Selectively Induces Human Prostate Cancer Cell Sensitivity to Oxidative Stress Through Modulation of NF-κB [J].
Cavazos, David A. ;
Price, Ramona S. ;
Apte, Shruti S. ;
deGraffenried, Linda A. .
PROSTATE, 2011, 71 (13) :1420-1428
[5]  
Chen XF, 2011, BMC HEALTH SERV RES, V11, DOI [10.1186/1472-6963-11-67, 10.1186/1472-6963-11-235]
[6]   MicroRNA-26a and-26b inhibit lens fibrosis and cataract by negatively regulating Jagged-1/Notch signaling pathway [J].
Chen, Xiaoyun ;
Xiao, Wei ;
Chen, Weirong ;
Liu, Xialin ;
Wu, Mingxing ;
Bo, Qu ;
Luo, Yan ;
Ye, Shaobi ;
Cao, Yihai ;
Liu, Yizhi .
CELL DEATH AND DIFFERENTIATION, 2017, 24 (08) :1431-1442
[7]   Ultraviolet B Radiation Stimulates the Interaction between Nuclear Factor of Activated T Cells 5 (NFAT5) and Nuclear Factor-Kappa B (NF-B) in Human Lens Epithelial Cells [J].
Chung, Inyoung ;
Hah, Young-Sool ;
Ju, SunMi ;
Kim, Ji-Hye ;
Yoo, Woong-Sun ;
Cho, Hee-Young ;
Yoo, Ji-Myong ;
Seo, Seong-Wook ;
Choi, Wan-Sung ;
Kim, Seong-Jae .
CURRENT EYE RESEARCH, 2017, 42 (07) :987-994
[8]   H2O2-mediated oxidative stress activates NF-κB in lens epithelial cells [J].
Dudek, EJ ;
Shang, F ;
Taylor, A .
FREE RADICAL BIOLOGY AND MEDICINE, 2001, 31 (05) :651-658
[9]   MicroRNA-34a promotes mitochondrial dysfunction-induced apoptosis in human lens epithelial cells by targeting Notch2 [J].
Fan, Fan ;
Zhuang, Jianhui ;
Zhou, Peng ;
Liu, Xin ;
Luo, Yi .
ONCOTARGET, 2017, 8 (66) :110209-110220