title: Inhibition of myeloperoxidase-mediated oxidative damage by nitrite in SH-SY5Y cells: Relevance to neuroprotection in neurodegenerative diseases.
abstract: Myeloperoxidase (MPO) and MPO-catalyzed hypochlorous acid (HOCl) is elevated in many neurodegenerative diseases, and lead to severe tissue injuries. Nitrite (NO2(-)) is a widespread inorganic molecule that has recently been proposed as a direct NO donor to exert antioxidant properties in vivo and vitro. Since NO2(-) and MPO (and/or HOCl) were important mediators in brain function and disease, we investigated the effects of NO2(-) on MPO-mediated damage to human neuroblastoma SH-SY5Y cells. Here, we showed that exposure of SH-SY5Y cells to MPO (or HOCl) resulted in a significant loss in viability, ATP and glutathione levels, and treatment of neuronal cells with NO2(-) substantially attenuated MPO (or HOCl)-dependent cellular toxicity. The protective effects of NO2(-) on MPO (or HOCl)-induced cytotoxicity were because that (1) NO2(-) at high concentrations competed effectively with Cl(-) for MPO, thus limiting OCl(-) production by the enzyme; (2) HOCl was removed by reacting with NO2(-), forming less damaging compound; (3) NO2(-) significantly inhibited MPO-mediated inactivation of brain protein (enolase) and protein oxidation. Therefore, NO2(-) could show novel protective effects in some neurodegenerative diseases by preventing MPO-mediated oxidative damage.
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China. Electronic address: naihaolu@jxnu.edu.cn.
authors.forename: Naihao
authors.initials: N
authors.lastname: Lu
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China. Electronic address: yiyuanpeng@yahoo.com.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Peng
mesh_terms: D055162:Biocatalysis; D045744:Cell Line, Tumor; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009573:Nitrites / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D009573:Nitrites; D006997:Hypochlorous Acid; D009195:Peroxidase
keywords: Anti-oxidant; MPO; Neurochemistry; Nitrite; Oxidative/nitrative stress