title: Nanomolar naloxone attenuates neurotoxicity induced by oxidative stress and survival motor neuron protein deficiency.
abstract: Oxidative stress and survival motor neuron (Smn) protein deficiency are the major causes of motor neuronal death. Naloxone exhibits neuroprotection against ischemic stroke and anti-inflammation. In this study, we determined whether nanomolar naloxone provides neuroprotection under oxidative stress (H(2)O(2)) and Smn deficiency in a motor neuron-like cell line, NSC34. In H(2)O(2)-treated NSC34 cells, naloxone (1-10 nM) increased cell survival and mitochondria membrane potential. In addition, naloxone decreased NADPH oxidase (NOX) 2 activation, reactive oxygen species production and oxygen consumption rate. Moreover, naloxone increased anti-apoptotic Bcl-2 expression, attenuated apoptotic protein (Bax, cytochrome c, and caspase) expression and decreased apoptotic death. Furthermore, naloxone also increased Smn mRNA and protein expression. In Smn knockdown NSC34 cells, Smn deficiency significantly increased H(2)O(2) cytotoxicity. Naloxone exhibited neuroprotection at higher concentrations in Smn knockdown NSC34 cells than in control cells. In conclusion, naloxone attenuated neurotoxicity induced by H(2)O(2) and Smn deficiency. Our findings also revealed the involvement of Smn protein in naloxone protection and oxidative stress-related neurotoxicity.
authors.affiliation: Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Hsu
authors.forename: Yuh-Jyh
authors.initials: YJ
authors.lastname: Jong
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Lin
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Tseng
authors.forename: Shih-Hsien
authors.initials: SH
authors.lastname: Hsu
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein; D009270:Naloxone; D010100:Oxygen
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