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Copper chaperone antioxidant-1, Atox-1, is involved in the induction of SOD3 in THP-1 cells

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Abstract

Superoxide dismutase (SOD) 3, a copper (Cu)-containing anti-oxidative enzyme, plays a key role in extracellular redox homeostasis. Cu chaperone antioxidant-1 (Atox-1) not only delivers Cu ions to SOD3 at the trans-Golgi network, it also functions as a transcription factor of SOD3; however, the role of Atox-1 in the regulation of SOD3 during the monocytic differentiation of THP-1 cells has not yet been elucidated. A treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the expression of the Cu transport protein ATP7A in THP-1 cells. On the other hand, the nuclear translocation of Atox-1 was detected in TPA-treated THP-1 cells, and was suppressed in the presence of the Cu chelator, bathocuproinedisulfonic acid. Furthermore, Atox-1 bound to the SOD3 promoter region in TPA-treated THP-1 cells. The overexpression of Atox-1 in THP-1 cells significantly enhanced TPA-elicited SOD3 expression, whereas its knockdown suppressed this induction. The present results demonstrate that Atox-1 functions as a key molecule in TPA-elicited SOD3 expression.

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Abbreviations

SOD:

Superoxide dismutase

Cu:

Copper

Atox-1:

Antioxidant-1

TPA:

12-O-tetradecanoylphorbol-13-acetate

BCS:

Bathocuproinedisulfonic acid

CCS:

Cu chaperone for SOD1

ChIP:

Chromatin immunoprecipitation

siRNA:

Small interfering RNA

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Acknowledgements

This study was supported in part by JSPS KAKENHI (to T.K.) [Grant Number 26460070] and a grant for the encouragement of young scientists from Gifu Pharmaceutical University (to T.K.).

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Authors and Affiliations

  1. Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan

    Tetsuro Kamiya, Kosuke Takeuchi, Saki Fukudome, Hirokazu Hara & Tetsuo Adachi

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  1. Tetsuro Kamiya
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  2. Kosuke Takeuchi
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  3. Saki Fukudome
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  4. Hirokazu Hara
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  5. Tetsuo Adachi
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Correspondence to Tetsuro Kamiya.

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Kamiya, T., Takeuchi, K., Fukudome, S. et al. Copper chaperone antioxidant-1, Atox-1, is involved in the induction of SOD3 in THP-1 cells. Biometals 31, 61–68 (2018). https://doi.org/10.1007/s10534-017-0067-1

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  • DOI: https://doi.org/10.1007/s10534-017-0067-1

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