D-galactose toxicity in mice is associated with mitochondrial dysfunction: protecting effects of mitochondrial nutrient R-alpha-lipoic acid.
D-galactose (D-gal) -induced aging models in Drosophila, houseflies, mice and rats have been widely used; however, the underlying mechanisms are poorly understood. To investigate the involvement of mitochondrial dysfunction of D-gal, mitochondrial function was examined in the brain and liver of C57BL/6J mice, subjected to a treatment of D-gal with or without a concomitant treatment with a mitochondrial nutrient, R-alpha-lipoic acid (LA). D-Gal treatment induced a significant decrease in succinate-linked respiratory control ratio (RCR) and ADP/O ratio in the liver and brain, and also a significant increase in the maximum velocity (Vmax) and substrate binding affinity (Km) of complex II in the liver. LA treatment to D-gal-injected animals restored mitochondrial RCR in both brain and liver, ADP/O and Km of complex II in the liver. These results suggest LA is effective in delaying D-gal toxicity by ameliorating mitochondrial dysfunction.
Long
Jiangang
J
Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Wang
Xuemin
X
Gao
Hongxiang
H
Liu
Zhi
Z
Liu
Changsheng
C
Miao
Mingyong
M
Cui
Xu
X
Packer
Lester
L
Liu
Jiankang
J
D000244:Adenosine Diphosphate / Q000378:metabolism; D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D045222:Electron Transport Chain Complex Proteins / Q000187:drug effects / Q000378:metabolism; D005690:Galactose / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D023421:Models, Animal; D010100:Oxygen / Q000378:metabolism; D011897:Random Allocation; D008063:Thioctic Acid / Q000494:pharmacology*
D045222:Electron Transport Chain Complex Proteins; D000244:Adenosine Diphosphate; D008063:Thioctic Acid; D010100:Oxygen; D005690:Galactose