title: Lipoamide Acts as an Indirect Antioxidant by Simultaneously Stimulating Mitochondrial Biogenesis and Phase II Antioxidant Enzyme Systems in ARPE-19 Cells.
abstract: In our previous study, we found that pretreatment with lipoamide (LM) more effectively than alpha-lipoic acid (LA) protected retinal pigment epithelial (RPE) cells from the acrolein-induced damage. However, the reasons and mechanisms for the greater effect of LM than LA are unclear. We hypothesize that LM, rather than the more direct antioxidant LA, may act more as an indirect antioxidant. In the present study, we treated ARPE-19 cells with LA and LM and compared their effects on activation of mitochondrial biogenesis and induction of phase II enzyme systems. It is found that LM is more effective than LA on increasing mitochondrial biogenesis and inducing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its translocation to the nucleus, leading to an increase in expression or activity of phase II antioxidant enzymes (NQO-1, GST, GCL, catalase and Cu/Zn SOD). Further study demonstrated that mitochondrial biogenesis and phase II enzyme induction are closely coupled via energy requirements. These results suggest that LM, compared with the direct antioxidant LA, plays its protective effect on oxidative damage more as an indirect antioxidant to simultaneously stimulate mitochondrial biogenesis and induction of phase II antioxidant enzymes.
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China; Department of Basic Science and Craniofacial Biology, College of Dentistry, New York University, New York, NY, United States of America.
authors.forename: Zhongbo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China; California Institute for Biomedical Research, La Jolla, CA, United States of America.
authors.forename: Haiqun
authors.initials: H
authors.lastname: Jia
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China; Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport, Tianjin, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China; Institute for Cancer Medicine, Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: Xuesen
authors.initials: X
authors.lastname: Li
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics; D004579:Electron Transport; D004798:Enzymes / Q000378:metabolism*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D001678:Organelle Biogenesis; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D004798:Enzymes; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D014157:Transcription Factors; D008063:Thioctic Acid; C013091:lipoamide