Protection of mitochondrial integrity from oxidative stress by the triaminopyridine derivative flupirtine

FEBS Letters

Struy, Heinz¹  Schlüter, Thomas²  Schönfeld, Peter² 

[1] Institute for Immunology, Medical Faculty, Otto-von-Guericke-University, Leipziger Straße 44, 39120 Magdeburg, Germany;Institute for Biochemistry, Medical Faculty, Otto-von-Guericke-University, Leipziger Straße 44, 39120 Magdeburg, Germany

关键词: Mitochondrion;    Oxidative stress;    Electron spin resonance spectroscopy;    Flupirtine;    ADP/ATP antiporter;    Permeability transition;    ANT;    ADP/ATP antiporter;    TBARS;    thiobarbituric acid reactive substances;    MAL-6;    4-maleimido-2;    2;    6;    6-tetramethylpiperidine-1-oxyl;    DMPO;    5;    5-dimethyl-1-pyrrolidine-N-oxide;    EDTA;    ethylene diamine tetraacetic acid;    ESR;    electron spin resonance spectroscopy;    RCR;    respiratory control ratio;    RLM;    rat liver mitochondria;    ROS;    reactive oxygen species;    EC50%;    effector concentration;    PT;    permeability transition;   

DOI  :  10.1016/S0014-5793(00)01923-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The suitability of the triaminopyridine derivative flupirtine, an analgesic drug with antioxidative property [Gassen, M., Pergande, G. and Youdim, M.B.H. (1998) Biochem. Pharmacol. 56, 1323–1329], for the preservation of mitochondrial integrity from oxidative stress-induced damage was studied. Rat liver mitochondria were exposed to strong oxidative stress as generated by Fe²⁺ plus ascorbate. Peroxidation damage of membrane lipids was followed by the measurement of thiobarbituric acid reactive substances. Protein oxidation was estimated by electron spin resonance spectroscopy, after labeling of the ‘peroxidized’ mitochondria with 4-maleimido-2,2,6,6-tetramethylpiperidine-1-oxyl. We found that (i) low concentrations of flupirtine (10 μM) protect lipids and also proteins (with lesser efficiency) from attacks of reactive oxygen species; (ii) flupirtine remarkably delayed the decline of complex mitochondrial functions, such as the respiratory control or the Ca²⁺ retention capacity of mitochondria, under oxidative stress; and (iii) the ADP/ATP antiporter (ANT), a main component of the oxidative phosphorylation machinery as well as a core component of the permeability transition pore complex, seems to be a membrane protein particularly protected by flupirtine. In conclusion, the preservation of the Ca²⁺ buffer capacity of mitochondria and of the ANT activity against oxidative stress supports an antiapoptotic application of flupirtine.

【 授权许可】

Unknown