文献类型：期刊文献

英文题名：Methylglyoxal produced by tumor cells through formaldehyde-enhanced Warburg effect potentiated polarization of tumor-associated macrophages

作者：Ma, Huijuan[1];Ding, Zhaoqian[1];Xie, Ying[1];Li, Linyi[1];Li, Dan[1];Lou, Kaiyan[1];Wang, Wei[2];Xu, Huan[1]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Univ Arizona, BIO5 Inst, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA

年份：2022

卷号：438

外文期刊名：TOXICOLOGY AND APPLIED PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000789999300003)】；

基金：Acknowledgements This work was funded by National Natural Science Foundation of China [grant No. 42177417 to H. X., grant No. 21906057 to H. X., grant No. 21738002 to W. W., grant No. 21577037 to K. L.] . This work was also funded by Shanghai Science and Technology Committee through Shanghai Sailing Program [grant No. 19YF1412500 to H. X.] and the Shanghai Natural Science Fund [grant No. 20ZR1414700 to K. L.] . This work was also funded by Shanghai Frontiers Science Center of Opto-genetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) [grant No. 2021 Sci & Tech 03-28] . The manuscript is dedicated to Dr. Scott Burchiel, and Huan Xu and Wei Wang would like to express deep gratitude to him for his long-lasting support as a mentor, colleague and friend.

语种：英文

外文关键词：Methylglyoxal; Formaldehyde; Tumor-associated macrophages; Warburg effect; Polarization; HIF-1a

摘要：Environmental exposure to formaldehyde is known to be associated with cancers and many other diseases. Although formaldehyde has been classified as a group I carcinogen, the molecular mechanisms of its carcinogenicity are still not fully understood. Formaldehyde is also involved in the folate-driven one-carbon metabolism, and excess amount of formaldehyde was found to interfere with other metabolic pathways including glycolysis, which can enhance Warburg effect and induce immunosuppression in tumor microenvironment. Therefore, different tumor cells and THP-1 derived macrophages were utilized to explore the metabolism-related effects induced by formaldehyde at environmentally relevant concentrations. Significant increases of glucose uptake, glycolysis levels, HIF-1 alpha signaling and methylglyoxal production were observed in tumor cells treated with 20 and 50 mu M formaldehyde for 24 h, and the overproduced methylglyoxal in the conditioned medium collected from the tumor cells treated with formaldehyde triggered macrophage polarization towards M2 cells. Myricetin, a flavonol scavenging methylglyoxal, reversed the polarization of macrophages induced by methylglyoxal at 50 mu M. These results not only provided essential evidences to reveal the molecular mechanisms of Warburg effect and metabolism-related immunosuppression related to formaldehyde exposure, but also indicated that methylglyoxal could be utilized as a target for therapeutic treatment or prevention of formaldehyde-induced immunotoxicity.