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. 2018 May 16;19(5):1486. doi: 10.3390/ijms19051486

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© 2018 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Regulation of Cu(I) and cDDP transports by the redox mechanism. The biosynthesis of GSH which plays important roles in redox regulation of Cu(I) and cDDP transport is shown here. The substrates of γGCS are glutamine and cysteine which are transported by xCT. GSH is oxidized to GSSG by Gpx and GSSG is reduced back to GSH by Gred. GSH can facilitate Cu(I) and Pt(II) delivery to Atox1 and ATP7A/ATP7B. GSH can upregulate hCtr1 expression because of its chelation with Cu(I). GSSG and Pt-GS conjugate can be transported by the MRP2 efflux pump. Abbreviations: xCT, cysteine-glutamine anti-polar transporter; Gpx, glutathione peroxidase; GS, glutathione synthetase; γGCS, γ-glutamylcysteine synthetase; Gred, glutathione reductase; MRP2, multidrug resistance protein 2.