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Light-induced disulfide dimerization of recoverin under ex vivo and in vivo conditionsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 июля 2015 г.
- Авторы: Zernii Evgeni Yu, Nazipova Aliya A., Gancharova Olga S., Kazakov Alexey S., Serebryakova Marina V., Zinchenko Dmitry V., Tikhomirova Natalya K., Senin Ivan I., Philippov Pavel P., Permyakov Eugene A., Permyakov Sergei E.
- Журнал: Free Radical Biology and Medicine
- Том: 83
- Год издания: 2015
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 283
- Последняя страница: 295
- DOI: 10.1016/j.freeradbiomed.2015.03.001
- Аннотация: Despite vast knowledge of the molecular mechanisms underlying photochemical damage of photoreceptors, linked to progression of age-related macular degeneration, information on specific protein targets of the light-induced oxidative stress is scarce. Here, we demonstrate that prolonged intense illumination (halogen bulb, 1500lx, 1-5h) of mammalian eyes under ex vivo (cow) or in vivo (rabbit) conditions induces disulfide dimerization of recoverin, a Ca(2+)-dependent inhibitor of rhodopsin kinase. Western blotting and mass spectrometry analysis of retinal extracts reveals illumination time-dependent accumulation of disulfide homodimers of recoverin and its higher order disulfide cross-linked species, including a minor fraction of mixed disulfides with intracellular proteins (tubulins, etc.). Meanwhile, monomeric bovine recoverin remains mostly reduced. These effects are accompanied by accumulation of disulfide homodimers of visual arrestin. Histological studies demonstrate that the light-induced oxidation of recoverin and arrestin occurs in intact retina (illumination for 2h), while illumination for 5h is associated with damage of the photoreceptor layer. A comparison of ex vivo levels of disulfide homodimers of bovine recoverin with redox dependence of its in vitro thiol-disulfide equilibrium (glutathione redox pair) gives the lowest estimate of redox potential in rod outer segments under illumination from -160 to -155 mV. Chemical crosslinking and dynamic light scattering data demonstrate an increased propensity of disulfide dimer of bovine recoverin to multimerization/aggregation. Overall, the oxidative stress caused by the prolonged intense illumination of retina might affect rhodopsin desensitization via concerted disulfide dimerization of recoverin and arrestin. The developed herein models of eye illumination are useful for studies of the light-induced thiol oxidation of visual proteins.
- Добавил в систему: Серебрякова Марина Васильевна