Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 9, 2019
Previous Article Next Article

The production of reactive oxygen species enhanced with the reduction of menadione by active thioredoxin reductase

Author affiliations

Abstract

Cytosolic thioredoxin reductase (TXNRD1) is an important selenoprotein that participates in the reduction of thioredoxin and many other redox-related substrates. The enhancement of ROS production to cause cancer cell death is an effective anticancer strategy. Herein, we found that menadione substantially increased ROS generation via interaction with TXNRD1. To elucidate the mechanism behind this, various TXNRD1 mutant proteins were used to investigate the relationship between ROS production and the reaction between enzymes and menadione. A mutation at the C-terminal active site -GCUG of TXNRD1 to -GSSG or -GC, or the N-terminal active site C59S, C64S, or the deletion of the C-terminal 16 amino acid residues caused the loss of TXNRD1 activity needed for the reduction of menadione and therefore resulted in the loss of the ROS production ability of menadione. In contrast, the mutation of -GCUG to -GCCG resulted in an increase in the TXNRD1 activity towards the reduction of menadione, thus leading to an increase in ROS production. The co-treatment of the TXNRD1 inhibitor aurothioglucose and menadione could significantly alleviate the efficiency of ROS generation in vitro and increase the viability of A549 cells. Moreover, menadione could be reduced by the glutathione system and caused ROS production with less efficiency. These results demonstrate that TXNRD1 can serve as an effective source to generate ROS, which may provide a novel anticancer method based on the use of menadione.

Graphical abstract: The production of reactive oxygen species enhanced with the reduction of menadione by active thioredoxin reductase

Back to tab navigation

Article information


Submitted
23 May 2019
Accepted
11 Jul 2019
First published
11 Jul 2019

Metallomics, 2019,11, 1490-1497
Article type
Paper

The production of reactive oxygen species enhanced with the reduction of menadione by active thioredoxin reductase

J. Li, X. Zuo, P. Cheng, X. Ren, S. Sun, J. Xu, A. Holmgren and J. Lu, Metallomics, 2019, 11, 1490
DOI: 10.1039/C9MT00133F

Social activity

Search articles by author

Spotlight

Advertisements