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Quantitative relationship between inhibition of respiratory complexes and formation of reactive oxygen species in isolated nerve terminals
Author(s) -
Sipos Ildikó,
Tretter Laszlo,
AdamVizi Vera
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01513.x
Subject(s) - reactive oxygen species , rotenone , chemistry , antimycin a , respiratory chain , aconitase , mitochondrial respiratory chain , mitochondrial ros , endogeny , biophysics , mitochondrion , biochemistry , microbiology and biotechnology , biology
In this study reactive oxygen species (ROS) generated in the respiratory chain were measured and the quantitative relationship between inhibition of the respiratory chain complexes and ROS formation was investigated in isolated nerve terminals. We addressed to what extent complex I, III and IV,respectively, should be inhibited to cause ROS generation. For inhibition of complex I, III and IV, rotenone, antimycin and cyanide were used, respectively, and ROS formation was followed by measuring the activity of aconitase enzyme. ROS formation was not detected until complex III was inhibited by up to 71 ± 4%, above that threshold inhibition, decrease in aconitase activity indicated an enhanced ROS generation. Similarly, threshold inhibition of complex IV caused anaccelerated ROS production. By contrast, inactivation of complex I to a small extent (16 ± 2%) resulted in a significant increase in ROS formation, and no clear threshold inhibition could be determined. However, the magnitude of ROS generated at complex I when it is completely inhibited is smaller than that observed when complex III or complex IV was fully inactivated. Our findings may add a novel aspect to the pathology of Parkinson's disease, showing that a moderate level of complex I inhibition characteristic in Parkinson's disease leads to significant ROS formation. The amount of ROS generated by complex I inhibition is sufficient to inhibit in situ the activity of endogenous aconitase.