Regulation of Cytochrome c Peroxidase Activity by Nitric Oxide and Laser Irradiation

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A. N. Osipov^1*, G. O. Stepanov¹, Yu. A. Vladimirov², A. V. Kozlov³, and V. E. Kagan⁴

¹Department of Biophysics, Russian State Medical University, ul. Ostrovityanova 1, 117513 Moscow, Russia; fax: (495) 434-1174; E-mail: anosipov@yahoo.com

²Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky pr. 31/5, 117192 Moscow, Russia; E-mail: yuvlad@mail.ru

³Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstrasse 13, A-1200 Vienna, Austria; E-mail: andrey.kozlov@vu-wien.ac.at

⁴University of Pittsburgh, 100 Technology Dr., Suite 333, 15260 Pittsburgh, PA, USA; E-mail: vkagan@ceoh.pitt.edu

^* To whom correspondence should be addressed.

Received April 19, 2006; Revision received May 26, 2006

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Apoptosis can be induced by activation of so-called “death receptors” (extrinsic pathway) or multiple apoptotic factors (intrinsic pathway), which leads to release of cytochrome c from mitochondria. This event is considered to be a point of no return in apoptosis. One of the most important events in the development of apoptosis is the enhancement of cytochrome c peroxidase activity upon its interaction with cardiolipin, which modifies the active center of cytochrome c. In the present work, we have investigated the effects of nitric oxide on the cytochrome c peroxidase activity when cytochrome c is bound to cardiolipin or sodium dodecyl sulfate. We have observed that cytochrome c peroxidase activity, distinctly increased due to the presence of anionic lipids, is completely suppressed by nitric oxide. At the same time, nitrosyl complexes of cytochrome c, produced in the interaction with nitric oxide, demonstrated sensitivity to laser irradiation (441 nm) and were photolyzed during irradiation. This decomposition led to partial restoration of cytochrome c peroxidase activity. Finally, we conclude that nitric oxide and laser irradiation may serve as effective instruments for regulating the peroxidase activity of cytochrome c, and, probably, apoptosis.

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KEY WORDS: apoptosis, cytochrome c, cardiolipin, nitric oxide, laser irradiation, peroxidase activity

DOI: 10.1134/S0006297906100117

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