Biogerontology

, Volume 8, Issue 3, pp 373–381 | Cite as

d-Galactose toxicity in mice is associated with mitochondrial dysfunction: protecting effects of mitochondrial nutrient R-alpha-lipoic acid

  • Jiangang Long
  • Xuemin Wang
  • Hongxiang Gao
  • Zhi Liu
  • Changsheng Liu
  • Mingyong Miao
  • Xu Cui
  • Lester Packer
  • Jiankang Liu
Research Article
First Online:
Received:
Accepted:

Abstract

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.

Keywords

Aging d-Galactose R-alpha-Lipoic acid Mitochondrial dysfunction Succinate-linked respiratory chain 
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Notes

Acknowledgements

We are grateful to Dr. Elizabeth Head for giving critical comments and editing the English. This study was supported by an Oversea Scholars Award from the Chinese Academy of Sciences, a Hi-Sun Science and Technology Prize from Zhejiang Hi-Sun Pharmaceuticals, Inc., and the National Science Foundation of China (Grant 30171030, 30472175).

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Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Jiangang Long
    • 1
    • 2
  • Xuemin Wang
    • 1
    • 2
  • Hongxiang Gao
    • 1
  • Zhi Liu
    • 1
  • Changsheng Liu
    • 1
  • Mingyong Miao
    • 2
  • Xu Cui
    • 3
  • Lester Packer
    • 4
  • Jiankang Liu
    • 1
    • 5
  1. 1.Institute for Nutritional Science, Shanghai Institutes of Biological SciencesChinese Academy of SciencesShanghaiChina
  2. 2.Department of Biochemistry and Molecular Biology, College of Basic Medical SciencesSecond Military Medical UniversityShanghaiChina
  3. 3.Institute of GerontologyThe General Hospital of the PLABeijingChina
  4. 4.Department of Molecular Pharmacology and ToxicologyUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Institute for Brain Aging and DementiaUniversity of CaliforniaIrvineUSA

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