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Nanomolar Naloxone Attenuates Neurotoxicity Induced by Oxidative Stress and Survival Motor Neuron Protein Deficiency

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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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Acknowledgments

This study was supported by grant provided from the National Science Council of Taiwan to Y. C. L. (Grant number: NSC 99-2320-B-037-023-MY3).

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan

    Ya-Yun Hsu, Yu-Ting Lin & Yi-Ching Lo

  2. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

    Ya-Yun Hsu, Yuh-Jyh Jong, Shih-Hsien Hsu & Yi-Ching Lo

  3. Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

    Ya-Yun Hsu & Yuh-Jyh Jong

  4. Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

    Yu-Ting Tseng & Yi-Ching Lo

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  1. Ya-Yun Hsu
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  2. Yuh-Jyh Jong
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  3. Yu-Ting Lin
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  5. Shih-Hsien Hsu
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  6. Yi-Ching Lo
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Correspondence to Yi-Ching Lo.

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Hsu, YY., Jong, YJ., Lin, YT. et al. Nanomolar Naloxone Attenuates Neurotoxicity Induced by Oxidative Stress and Survival Motor Neuron Protein Deficiency. Neurotox Res 25, 262–270 (2014). https://doi.org/10.1007/s12640-013-9414-3

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  • DOI: https://doi.org/10.1007/s12640-013-9414-3

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