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

• DOI: 10.1007/s10534-017-0067-1
• Publication Date: 2017-11-22T08:53:30Z
• Authors: Tetsuro Kamiya; Kosuke Takeuchi; Saki Fukudome; Hirokazu Hara; Tetsuo Adachi
• Keywords: Cell Nucleus; 0301 basic medicine; Superoxide Dismutase; THP-1 Cells; Cell Differentiation; Monocytes; Metallochaperones; Protein Transport; 03 medical and health sciences; Copper Transport Proteins; Gene Expression Regulation; Copper-Transporting ATPases; Humans; RNA, Small Interfering; Promoter Regions, Genetic; Oxidation-Reduction; Copper; Chelating Agents; Molecular Chaperones; Phenanthrolines; Protein Binding; Signal Transduction

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.