Copper chaperone antioxidant-1, Atox-1, is involved in the induction of SOD3 in THP-1 cells
Copper chaperone antioxidant-1, Atox-1, is involved in the induction of SOD3 in THP-1 cells
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DOI：
10.1007/s10534-017-0067-1
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发表时间：
2018-02-01
期刊：
影响因子：
3.5
通讯作者：
Adachi, Tetsuo
中科院分区：
文献类型：
--
作者：
Kamiya, Tetsuro;Takeuchi, Kosuke;Adachi, Tetsuo
超氧化物歧化酶3是一种含铜的抗氧化酶，在细胞外氧化还原动态平衡中起着关键作用。铜伴侣抗氧化剂-1(Atox-1)不仅在跨高尔基网络将铜离子输送到SOD3，而且还作为SOD3的转录因子发挥作用；然而，Atox-1在THP-1细胞单核细胞分化过程中对SOD3的调控作用尚未阐明。12-O-十四酰佛波酯(TPA)诱导THP-1细胞铜转运蛋白ATP7A的表达。另一方面，在TPA处理的THP-1细胞中检测到Atox-1的核转位，并在铜络合剂偏铜丙二磺酸的存在下被抑制。此外，在TPA处理的THP-1细胞中，Atox-1与SOD3启动子区域结合。Atox-1在THP-1细胞中的过表达显著增强了TPA诱导的SOD3的表达，而其基因敲除则抑制了这种诱导。目前的结果表明，Atox-1在TPA诱导的SOD3表达中起关键作用。
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.