Lipoamide protects retinal pigment epithelial cells from oxidative stress and mitochondrial dysfunction.
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.
Li
Xuesen
X
Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Liu
Zhongbo
Z
Luo
Cheng
C
Jia
Haiqun
H
Sun
Lijuan
L
Hou
Bei
B
Shen
Weili
W
Packer
Lester
L
Cotman
Carl W
CW
Liu
Jiankang
J
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
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