Expression of the zinc transporter ZIP1 in osteoclasts
Expression of the zinc transporter ZIP1 in osteoclasts
复制标题
DOI：
10.1016/j.bone.2005.04.035
复制
发表时间：
2005-09-01
期刊：
影响因子：
4.1
通讯作者：
Gupta, A
中科院分区：
文献类型：
--
作者：
Khadeer, MA;Sahu, SN;Gupta, A
锌以前已被证明是一种有效的破骨细胞生成和破骨细胞功能的抑制剂。破骨细胞吸收锌的机制还没有被描述。我们已经证实了以前的研究中的破骨细胞生成的细胞外锌的存在下减少。我们证明，破骨细胞表达一个无处不在的质膜锌转运蛋白，即ZIP 1，这是弥漫性分布在整个细胞质。继腺病毒介导的ZIP 1在小鼠破骨细胞中的过度表达，ZIP 1主要与肌动蛋白在密封区共定位，并显着抑制破骨细胞的功能，通过再吸收活性评估。最后，ZIP 1的过度表达对NF-κ B B结合活性产生负面影响，如电泳迁移率变动分析所评估。总之，这些数据都证实了以前的研究，破骨细胞的形成和活性的锌的调节，并揭示了锌的吸收机制，发挥了重要的影响破骨细胞的活性的存在。(c)2005年爱思唯尔公司All rights reserved.
Zinc has been previously demonstrated to be a potent inhibitor of osteoclastogenesis and osteoclast function. The mechanisms for cellular uptake of zinc into osteoclasts have not been characterized. We have corroborated previous studies on the reduction of osteoclastogenesis in the presence of extracellular zinc. We demonstrate that osteoclasts express a ubiquitous plasma membrane zinc transporter, namely ZIP1, which was diffusely distributed throughout the cytoplasm. Following an adenoviral-mediated overexpression of ZIP1 in murine osteoclasts, ZIP1 was predominantly colocalized with actin at the sealing zone and significantly inhibited osteoclast function, as assessed by resorptive activity. Finally, overexpression of ZIP1 negatively impacted NF-kappa B binding activity, as assessed by electrophoretic mobility shift assays. In conclusion, these data both corroborate previous studies on regulation of osteoclast formation and activity by zinc and reveal the presence of a zinc uptake mechanism that exerts an important effect on osteoclast activity. (c) 2005 Elsevier Inc. All rights reserved.