title: Lipoamide protects retinal pigment epithelial cells from oxidative stress and mitochondrial dysfunction.
abstract: alpha-Lipoic acid (LA) has been widely studied as an agent for preventing and treating various diseases associated with oxidative disruption of mitochondrial functions. To investigate a related mitochondrial antioxidant, we compared the effects of lipoamide (LM), the neutral amide of LA, with LA for measures of oxidative damage and mitochondrial dysfunction in a human retinal pigment epithelial (RPE) cell line. Acrolein, a major component of cigarette smoke and a product of lipid peroxidation, was used to induce oxidative mitochondrial damage in RPE cells. Overall, using comparable concentrations, LM was more effective than LA at preventing acrolein-induced mitochondrial dysfunction and oxidative stress. Relative to LA, LM improved ATP levels, membrane potentials, and activities of mitochondrial complexes I, II, and V and dehydrogenases that had been decreased by acrolein exposure. LM reduced acrolein-induced oxidant generation, calcium levels, protein oxidation, and DNA damage to a greater degree than LA. And, total antioxidant capacity, glutathione content, glutathione S-transferase, and superoxide dismutase activities and expression of nuclear factor-E2-related factor 2 were increased by LM relative to LA. These results suggest that LM is a more potent mitochondrial-protective agent and antioxidant than LA in protecting RPE from oxidative damage.
authors.affiliation: Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xuesen
authors.initials: X
authors.lastname: Li
authors.forename: Zhongbo
authors.initials: Z
authors.lastname: Liu
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Haiqun
authors.initials: H
authors.lastname: Jia
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.forename: Bei
authors.initials: B
authors.lastname: Hou
authors.forename: Weili
authors.initials: W
authors.lastname: Shen
authors.forename: Lester
authors.initials: L
authors.lastname: Packer
authors.forename: Carl W
authors.initials: CW
authors.lastname: Cotman
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D000171:Acrolein / Q000494:pharmacology; D004249:DNA Damage; D005609:Free Radicals; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D018384:Oxidative Stress; D010857:Pigment Epithelium of Eye / Q000166:cytology*; D012906:Smoke; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D005609:Free Radicals; D012906:Smoke; D013778:Tetrazolium Salts; D013844:Thiazoles; D008063:Thioctic Acid; D000171:Acrolein; C013091:lipoamide; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; C022616:thiazolyl blue