title: Tetramethylpyrazine Protects Retinal Capillary Endothelial Cells (TR-iBRB2) against IL-1β-Induced Nitrative/Oxidative Stress.
abstract: Blood-retinal barrier (BRB) breakdown is one of the primary causes of diabetic retinopathy (DR). The pro-inflammatory factor interleukin-1β (IL-1β) was reported to be involved in the induction of BRB breakdown during the pathogenesis of DR. In the present study, we investigated the protective effect of tetramethylpyrazine (TMP), a major active component of the traditional herb Ligusticum chuanxiong, on IL-1β-induced cell death of the rat retinal capillary endothelial TR-iBRB2 cells. Our results showed that IL-1β-induced cell dysfunction in TR-iBRB2 cells via inducing nitrative/oxidative stress; however, such effect was attenuated with the pre-treatment of TMP. The cellular protective effect of TMP was likely to be mediated through the inhibition of inducible nitric oxide synthase (iNOS) expression and leukostasis as well as suppression of reactive oxygen species (ROS) generation, mitochondrial dysfunction and MAPKs activation. These findings significantly contribute to a better understanding of the protective effect of TMP in DR and form the basis of the therapeutic development of TMP in treating such disease in the future.
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. zhuxue@jsinm.org.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. wangke@jsinm.org.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. zhangkai@jsinm.org.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Wuxi No. 2 People's Hospital, Nanjing Medical University, Wuxi 214002, China. doctxh001@gmail.com.
authors.forename: Xuhua
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Ophthalmology, Wuxi No. 2 People's Hospital, Nanjing Medical University, Wuxi 214002, China. wuzhifeng248@gmail.com.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Wuxi No. 2 People's Hospital, Nanjing Medical University, Wuxi 214002, China. doctxh001@gmail.com.
authors.forename: Song
authors.initials: S
authors.lastname: Sun
authors.affiliation: Faculty of Pharmacy, University of Sydney, New South Wales 2006, Australia. fanfan.zhou@sydney.edu.au.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Save Sight Institute, University of Sydney, New South Wales 2000, Australia. ling.zhu@sydney.edu.au.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001813:Blood-Retinal Barrier / Q000187:drug effects* / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D020011:Protective Agents / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D009566:Nitrates; D020011:Protective Agents; D011719:Pyrazines; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases; C017953:tetramethylpyrazine
keywords: TR-iBRB2 cells; nitrosative stress; oxidative stress; tetramethylpyrazine