| Title | Aldehyde dehydrogenase 1A1 increases NADH levels and promotes tumor growth via glutathione/dihydrolipoic acid-dependent NAD(+) reduction |
| Authors | Wang, Baiyun Chen, Xue Wang, Zixi Xiong, Wei Xu, Tao Zhao, Xinyuan Cao, Yang Guo, Yanru Li, Lin Chen, She Huang, Song Wang, Xiaodong Fang, Min Shen, Zhirong |
| Affiliation | Tsinghua Univ, Sch Life Sci, Peking Univ, Natl Inst Biol Sci,Joint Grad Program, Beijing 100084, Peoples R China. Peking Univ, Joint Ctr Life Sci, Beijing 100871, Peoples R China. Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China. Natl Inst Biol Sci, Beijing 102206, Peoples R China. Peking Univ, Joint Ctr Life Sci, Beijing 100871, Peoples R China. Fang, M (reprint author), Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China. Shen, ZR (reprint author), Natl Inst Biol Sci, Beijing 102206, Peoples R China. |
| Keywords | aldehyde dehydrogenase lung cancer glutathione dihydrolipoic acid NAD(+)/NADH ratio SELECTIVE INHIBITORS OXIDATIVE STRESS BREAST-CANCER RETINOIC ACID LUNG-CANCER STEM-CELLS VITAMIN-E ALDH1A1 ALDH3A1 METABOLISM |
| Issue Date | 2017 |
| Publisher | ONCOTARGET |
| Citation | ONCOTARGET.2017,8(40),67043-67055. |
| Abstract | Aldehyde dehydrogenase 1A1 (ALDH1A1) is a member of the aldehyde dehydrogenase superfamily that oxidizes aldehydes to their corresponding acids, reactions that are coupled to the reduction of NAD(+) to NADH. We report here that ALDH1A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD(+) to NADH. The GSH/DHLA-dependent NAD(+)-reduction activity of ALDH1A1 is not affected by the aldehyde dehydrogenase inhibitor or by mutation of the residues in its aldehyde-binding pocket. It is thus a distinct biochemical reaction from the classic aldehyde-dehydrogenase activity catalyzed by ALDH1A1. We also found that the ectopic expression of ALDH1A1 decreased the intracellular NAD(+)/NADH ratio, while knockout of ALDH1A1 increased the NAD+/NADH ratio. Simultaneous knockout of ALDH1A1 and its isozyme ALDH3A1 in lung cancer cell line NCI-H460 inhibited tumor growth in a xenograft model. Moreover, the ALDH1A1 mutants that retained their GSH/DHLA-dependent NAD(+) reduction activity but lost their aldehyde-dehydrogenase activity were able to decrease the NAD(+)/NADH ratio and to rescue the impaired growth of ALDH1A1/3A1 double knockout tumor cells. Collectively, these results suggest that this newly characterized GSH/DHLA-dependent NAD(+)-reduction activity of ALDH1A1 can decrease cellular NAD(+)/NADH ratio and promote tumor growth. |
| URI | http://hdl.handle.net/20.500.11897/470844 |
| ISSN | 1949-2553 |
| DOI | 10.18632/oncotarget.17688 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 |
