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Neurotoxicity Research

, Volume 25, Issue 3, pp 262–270 | Cite as

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

  • Ya-Yun Hsu
  • Yuh-Jyh Jong
  • Yu-Ting Lin
  • Yu-Ting Tseng
  • Shih-Hsien Hsu
  • Yi-Ching Lo
Original Article

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.

Keywords

Naloxone Oxidative stress Survival motor neuron protein Neurotoxicity 

Notes

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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ya-Yun Hsu
    • 1
    • 2
    • 3
  • Yuh-Jyh Jong
    • 2
    • 3
  • Yu-Ting Lin
    • 1
  • Yu-Ting Tseng
    • 4
  • Shih-Hsien Hsu
    • 2
  • Yi-Ching Lo
    • 1
    • 2
    • 4
  1. 1.Department of Pharmacology, School of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  2. 2.Graduate Institute of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  3. 3.Department of PediatricsKaohsiung Medical University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan
  4. 4.Graduate Institute of Natural ProductsKaohsiung Medical UniversityKaohsiungTaiwan

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