Cytochrome c as a facultative enzyme – lipoperoxidase and it’s inhibition by antioxidants
Romodin, L. A.; Vladimirov, Y. A.; Lysenko, N. P.; Chernetsov, V. B.; Antonova, E.
Show abstract
Many researchers consider a key role in initiation of apoptosis along the mitochondrial pathway to be enhanced by cytochrome c, one of the components of the mitochondrial respiratory chain, which acquires peroxidase activity by forming a complex with phospholipids. Mitochondrial membranes are destroyed affected by the peroxidase reaction catalyzed by this supramolecular nanoparticle, resulting in the release of various proapoptotic factors into the cellular cytoplasm, ultimately leading to the development of an apoptosis pathway. The study of lipoperoxidase activity of the cytochrome c with cardiolipin complex is conducted via activated chemiluminescence. However, prior to this study, no assessment of the potential contribution of free non-heme iron, which can be inserted into the sample, into chemiluminescence of the system of cytochrome c complex with cardiolipin- hydrogen peroxide. It was found during the study process, that chemiluminescence of this system is indeed generated by the activity of the cytochrome c with cardiolipin complex, and the method of activated chemiluminescence is actually suitable for its study. The effect of trolox and dihydroquercetin (taxifolin) as synthetic and natural antioxidants on lipoperoxidase activity of the cytochrome c with cardiolipin complex was as well assessed via application of chemiluminescence activator specific for lipid peroxidation reactions - coumarin-334. A complete inhibition of lipoperoxidase activity for a few minutes with its subsequent full development under the trolox response and its dose-dependent uniform decrease under dihydroquercetin effect was obtained. These findings are promising for the future studies on inhibition of lipoperoxidase activity of this nanoparticle by antioxidants in order to inhibit the inappropriate apoptosis. Peroxidase activity of intact mitochondria in the comparative application of two chemiluminescence activators: coumarin-334 and coumarin-525, was also featured. Significance of the studyThis study proves that the method of activated chemiluminescence is adequate to study the processes occurring in the early stages of apoptosis. Inhibition of lipoperoxidase activity of the cytochrome c with cardiolipin complex by antioxidants was demonstrated. These findings prove that studies on the effect of antioxidants on this supramolecular nanoparticle will eventually lead to discovery of the news means to prevent and treat diseases caused by apoptosis: myocardial infarction, Alzheimers disease, Parkinsons disease, etc.
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