Redox status of neuronal calcium sensor proteins in photoreceptor systemстатья Тезисы

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Дата последнего поиска статьи во внешних источниках: 22 февраля 2019 г.

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[1] Redox status of neuronal calcium sensor proteins in photoreceptor system / V. Baksheeva, N. Gotmanova, N. Tikhomirova et al. // FEBS open bio. — 2018. — Vol. 8, no. 1. — P. 354. In the retina, high metabolic activity and abundance of photosensitized reactions contribute to elevated risk of oxidative stress causing photoreceptor loss and irreversible vision deterioration. Here, we demonstrate that oxidative stress of photoreceptors is associated with alterations in redox status of neuronal calcium sensors (NCSs), signaling proteins regulating various aspects of neuronal function. Western blotting and mass­spectrometry analysis revealed accumulation of oxidized monomers, disulfide dimers and multimers of NCSs involving their conserved cysteine residue under cellular, ex vivo, and in vivo conditions. NCSs oxidation precedes and accompanies light­induced damage of photoreceptors and results in decline in retinal content of some of these proteins. Disulfide dimerization of NCSs is also observed in intact retina suggesting their redox regulation. As exemplified by recoverin and NCS1, NCSs exhibit different susceptibility to oxidation depending on intracellular conditions. The results of in vitro oxidation assay and Ellman’s test demonstrate that Ca2+ binding potentiates thiol oxidation of recoverin, but inhibits it in the case of NCS1 that instead oxidizes in apo­ or Zn2+­bound states. Furthermore, the thiol oxidation differently affects structural features and function of these proteins. Using disulfide dimers and oxidation mimicking mutants it was demonstrated that the oxidation inhibits photoreceptor membrane association of recoverin, but not of NCS1. In addition, it produces constitutively active recoverin and enhances activity of Ca2+­NCS1 in regulation of rhodopsin desensitization by GRK1. Overall, NCSs represent redox­sensitive proteins that may undergo redox regulation in normal photoreceptors and exhibit pronounced structural and functional changes in oxidative stress, what possibly contributes to pathogenesis of neuro­ophthalmological disorders. The study was supported by Russian Foundation for Basic Research (grant #18­-04­-01250). [ DOI ]

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