Label-free LC-MS/MS proteomics analyses reveal proteomic changes in oxidative stress and the SOD antioxidant strategy in TM cells

被引:6
作者
Li, Qian [1 ]
Zhang, Liyu [1 ]
Xu, Yuxin [1 ]
机构
[1] Anhui Med Univ, Dept Ophthalmol, Affiliated Hosp 2, Hefei 230601, Anhui, Peoples R China
关键词
Trabecular meshwork cells; Oxidative stress; Label-free; Proteomic analysis; SOD; MITOCHONDRIAL DYSFUNCTION; TGF-BETA; DAMAGE;
D O I
10.1186/s12014-022-09350-4
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Background Treatment for glaucoma has traditionally been limited to reducing intraocular pressure (IOP). Inhibiting oxidative stress in the trabecular meshwork (TM) is regarded as a new treatment for glaucoma; however, the effects do not meet expectations. Exploring the mechanism by which oxidative stress and antioxidant stress occur in TM cells will offer clues to aid the development of new treatments. Methods and results In our study, we cultured TM cells and used H2O2 and SOD to induce and inhibit oxidative stress, respectively. Label-free LC-MS/MS quantitative proteomic analysis was conducted to analyze the differentially expressed proteins and relevant signaling pathways. A total of 24 upregulated proteins and 18 downregulated proteins were identified under oxidative stress. PTGS2, TGF beta r2 and ICAM-1 are the key proteins. The PTGS2/NF-kappa b pathway, TGF-beta/Smad signaling pathway and AGE-RAGE signaling pathway in diabetic complications may be the major signaling pathways under conditions of ROS-induced damage in TM cells. Seventy-eight proteins were upregulated and 73 proteins were downregulated under antioxidant stress in TM cells. The key protein was ICAM-1, which participates in the African trypanosomiasis pathway, one of the most important pathways under antioxidant stress. Combining the results of the Venn diagram with protein-protein interactions (PPIs), ICAM-1 was identified as the major protein. Cell Counting Kit-8 (CCK-8) and western blotting (WB) were used to reveal that suppressing the expression of ICAM-1 would improve the survival of TM cells. Conclusions Key proteins and signaling pathways play important roles in the mechanisms of oxidative stress and antioxidant strategies in TM cells. ICAM-1 knockdown can suppress the apoptosis of TM cells induced by H2O2, which may reveal new therapeutic targets and biomarkers for glaucoma.
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页数:16
相关论文
共 26 条
[1]   Oregano (Origanum vulgare L.) essential oil provides anti-inflammatory activity and facilitates wound healing in a human keratinocytes cell model [J].
Avola, Rosanna ;
Granata, Giuseppe ;
Geraci, Corrada ;
Napoli, Edoardo ;
Graziano, Adriana Carol Eleonora ;
Cardile, Venera .
FOOD AND CHEMICAL TOXICOLOGY, 2020, 144
[2]   ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis [J].
Bui, Triet M. ;
Wiesolek, Hannah L. ;
Sumagin, Ronen .
JOURNAL OF LEUKOCYTE BIOLOGY, 2020, 108 (03) :787-799
[3]   Protective effects of Salvia miltiorrhiza on adenine-induced chronic renal failure by regulating the metabolic profiling and modulating the NADPH oxidase/ROS/ERK and TGF-β/Smad signaling pathways [J].
Cai, Hongdie ;
Su, Shulan ;
Li, Yonghui ;
Zeng, Huiting ;
Zhu, Zhenhua ;
Guo, Jianming ;
Zhu, Yue ;
Guo, Sheng ;
Yu, Li ;
Qian, Dawei ;
Tang, Yuping ;
Duan, Jinao .
JOURNAL OF ETHNOPHARMACOLOGY, 2018, 212 :153-165
[4]   α-Lipoic Acid Antioxidant Treatment Limits Glaucoma-Related Retinal Ganglion Cell Death and Dysfunction [J].
Inman, Denise M. ;
Lambert, Wendi S. ;
Calkins, David J. ;
Horner, Philip J. .
PLOS ONE, 2013, 8 (06)
[5]   Efficacy of valproic acid for retinitis pigmentosa patients: a pilot study [J].
Iraha, Satoshi ;
Hirami, Yasuhiko ;
Ota, Sachiko ;
Sunagawa, Genshiro A. ;
Mandai, Michiko ;
Tanihara, Hidenobu ;
Takahashi, Masayo ;
Kurimoto, Yasuo .
CLINICAL OPHTHALMOLOGY, 2016, 10 :1375-1384
[6]   Sensitivity of Ocular Anterior Chamber Tissues to Oxidative Damage and Its Relevance to the Pathogenesis of Glaucoma [J].
Izzotti, Alberto ;
Sacca, Sergio C. ;
Longobardi, Mariagrazia ;
Cartiglia, Cristina .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2009, 50 (11) :5251-5258
[7]  
Jiang WM, 2016, AM J TRANSL RES, V8, P799
[8]   Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma [J].
Jiang, Ying ;
Sun, Aihua ;
Zhao, Yang ;
Ying, Wantao ;
Sun, Huichuan ;
Yang, Xinrong ;
Xing, Baocai ;
Sun, Wei ;
Ren, Liangliang ;
Hu, Bo ;
Li, Chaoying ;
Zhang, Li ;
Qin, Guangrong ;
Zhang, Menghuan ;
Chen, Ning ;
Zhang, Manli ;
Huang, Yin ;
Zhou, Jinan ;
Zhao, Yan ;
Liu, Mingwei ;
Zhu, Xiaodong ;
Qiu, Yang ;
Sun, Yanjun ;
Huang, Cheng ;
Yan, Meng ;
Wang, Mingchao ;
Liu, Wei ;
Tian, Fang ;
Xu, Huali ;
Zhou, Jian ;
Wu, Zhenyu ;
Shi, Tieliu ;
Zhu, Weimin ;
Qin, Jun ;
Xie, Lu ;
Fan, Jia ;
Qian, Xiaohong ;
He, Fuchu ;
Zhu, Yunping ;
Wang, Yi ;
Yang, Dong ;
Liu, Wanlin ;
Liu, Qiongming ;
Yang, Xiaoming ;
Zhen, Bei ;
Wu, Zhenyu ;
Fan, Jia ;
Sun, Huichuan ;
Qian, Juying ;
Hong, Tao .
NATURE, 2019, 567 (7747) :257-+
[9]   Inhibitory Effect of Astaxanthin on Oxidative Stress-Induced Mitochondrial Dysfunction-A Mini-Review [J].
Kim, Suhn Hyung ;
Kim, Hyeyoung .
NUTRIENTS, 2018, 10 (09)
[10]   Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis [J].
Kimura, Atsuko ;
Namekata, Kazuhiko ;
Guo, Xiaoli ;
Noro, Takahiko ;
Harada, Chikako ;
Harada, Takayuki .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2017, 2017