Multi-omics analyses of red blood cell reveal antioxidation mechanisms associated with hemolytic toxicity of gossypol

文献类型： 外文期刊

第一作者： Tang, Chaohua

作者： Tang, Chaohua;Meng, Qingshi;Zhang, Kai;Zhan, Tengfei;Zhao, Qingyu;Zhang, Junmin;Tang, Chaohua;Meng, Qingshi;Zhang, Kai;Zhan, Tengfei;Zhao, Qingyu;Zhang, Junmin;Zhang, Sheng

作者机构：

关键词： gossypol;red blood cell;hemolytic toxicity;metabolomics;proteomics

期刊名称：ONCOTARGET （ 影响因子：5.168； 五年影响因子：5.312 ）

ISSN： 1949-2553

年卷期： 2017 年 8 卷 61 期

页码：

收录情况： SCI

摘要： Gossypol is an antiproliferative drug with limited use due to its hemolytic toxicity. In this study, accelerated hemolysis was observed in the cows treated with gossypol. Comparative metabolomics were used to gain responsive pathways in the red blood cell (RBC) to the treatment, which were crossly validated by parallel iTRAQ-based proteomic analysis and enzyme activity assay. We found that gossypol treatment appeared to considerably activate pentose phosphate pathway (PPP) with an increased key product of ribose-5-phosphate and the increased abundance and activity of several key enzymes such as 6-phosphogluconate dehydrogenase, flavin reductase, and ribose-phosphate pyrophesphokinase. Meanwhile, a decreased glycolysis metabolism was observed, as many input metabolites of glycolysis were reduced in the gossypol group, whereas its distal metabolites were unchanged, along with decreased abundance of triosephosphate isomerase and increased abundance of enzymes catalyzing several distal glycolytic steps. Oxidative reduction pathways were also remarkably affected as we found a decreased substrate of flavin reductase, glutathione disulfide, increased glutathione reductase activity, and increased abundance and activity of glutathione S-transferase with the increase of its catalytic product, cysteine. Our results demonstrated that glycolysis, PPP, and oxidative reduction pathways of RBC were all involved in RBC's response to the hemolytic toxicity of gossypol.

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