Nanomolar Naloxone Attenuates Neurotoxicity Induced by Oxidative Stress and Survival Motor Neuron Protein Deficiency |
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Authors: | Ya-Yun Hsu Yuh-Jyh Jong Yu-Ting Lin Yu-Ting Tseng Shih-Hsien Hsu Yi-Ching Lo |
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Institution: | 1. Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan 2. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan 3. Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan 4. Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
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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 (H2O2) and Smn deficiency in a motor neuron-like cell line, NSC34. In H2O2-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 H2O2 cytotoxicity. Naloxone exhibited neuroprotection at higher concentrations in Smn knockdown NSC34 cells than in control cells. In conclusion, naloxone attenuated neurotoxicity induced by H2O2 and Smn deficiency. Our findings also revealed the involvement of Smn protein in naloxone protection and oxidative stress-related neurotoxicity. |
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