Control of Trx1 redox state modulates protection against methyl methanesulfonate-induced DNA damage via stabilization of p21

Gu, Li H.; Gao, Wei; Yang, Hui; Wang, Bei Bei; Wang, Xiao Na; Xu, Jianguo; Zhang, Hong

doi:10.1093/jb/mvv080

Cited by 5 publications

(1 citation statement)

References 42 publications

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“…The overexpression of the Trx1 gene activated hypoxic induction factor 1 (HIF-1α) in cancer cells, increasing VEGF expression [ 45 , 46 ] and promoting tumour angiogenesis, which leads to tumour invasion and metastasis [ 47 ]. Overexpressed Trx1 was involved in DNA damage by stabilizing p21 expression and being associated with haematological system diseases [ 48 ]. Following inhibition of Trx1 expression, leukaemia cell cycle was blocked [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Compound kushen injection suppresses human acute myeloid leukaemia by regulating the Prdxs/ROS/Trx1 signalling pathway

Jin

Yang

et al. 2018

J Exp Clin Cancer Res

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BackgroundThe increase in the levels of reactive oxygen species (ROS) in acute myeloid leukemia (AML) patients has been previously described; thus, it is important to regulate ROS levels in AML.MethodsFlow cytometry were used to assess the in vitro effect of compound kushen injection (CKI). Quantitative proteomics were used to analyse the mechanism. The AML patient-derived xenograft (PDX) model were used to evaluate the in vivo effect of CKI.ResultsWe found that intracellular ROS levels in AML cells were decreased, the antioxidant capacity were increased when treated with CKI. CKI inhibited the proliferation of AML cells and enhanced the cytotoxicity of AML cells, which has few toxic effects on haematopoietic stem cells (HSCs) and T cells. At the single-cell level, individual AML cells died gradually by CKI treatment on optofluidic chips. CKI promoted apoptosis and arrested cell cycle at G1/G0 phase in U937 cells. Furthermore, higher peroxiredoxin-3 (Prdx3) expression levels were identified in CKI-treated U937 cells through quantitative proteomics detection. Mechanically, the expression of Prdx3 and peroxiredoxin-2 (Prdx2) was up-regulated in CKI-treated AML cells, while thioredoxin 1 (Trx1) was reduced. Laser confocal microscopy showed that the proteins Prdx2 could be Interacted with Trx1 by CKI treatment. In vivo, the survival was longer and the disease was partially alleviated by decreased CD45+ immunophenotyping in peripheral blood in the CKI-treated group in the AML PDX model.ConclusionsAntioxidant CKI possess better clinical application against AML through the Prdxs/ROS/Trx1 signalling pathway.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0948-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Compound kushen injection suppresses human acute myeloid leukaemia by regulating the Prdxs/ROS/Trx1 signalling pathway

Jin

Yang

et al. 2018

J Exp Clin Cancer Res

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Comet assay: an essential tool in toxicological research

2016

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The comet assay is a versatile, reliable, cost-efficient, and fast technique for detecting DNA damage and repair in any tissue. It is useable in almost any cell type and applicable to both eukaryotic and prokaryotic organisms. Instead of highlighting one of the numerous specific aspects of the comet assay, the present review aims at giving an overview about the evolution of this widely applicable method from the first description by Ostling and Johanson to the OECD Guideline 489 for the in vivo mammalian comet assay. In addition, methodical aspects and the influence of critical steps of the assay as well as the evaluation of results and improvements of the method are reviewed. Methodical aspects regarding oxidative DNA damage and repair are also addressed. An overview about the most recent works and relevant cutting-edge reviews based on the comet assay with special regard to, e.g., clinical applications, nanoparticles or environmental risk assessment concludes this review. Taken together, the presented overview raises expectations to further decades of successful applications and enhancements of this excellent method.

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