Study of the fullerene C60 interaction with aryl-hydrocarbon receptor

Study of the fullerene C60 interaction with aryl-hydrocarbon receptor

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    Taking into account pseudo-aromatic structure of the C60 and the similarity of its effects with those when acting on the aryl-hydrocarbon receptor (AhR) with aromatic molecules, we hypothesize that fullerene is capable of specific targeting AhR. These receptors are very widely represented in vertebrates, especially in the skin and mucous tissues, and are ligand-dependent transcription factors that regulate different biological processes. AhR is activated by viral infection inhibiting the interferon production, but the AhR antagonists suppress viral replication. It is important, the NRF2 (the main transcription factor of antioxidants) is triggered also through the AhR signaling suppressing reactive oxygen species generation.

    The purpose of the study was to estimate AHR and NRF2 expression in the human melanoma and U-937 cells after their treatment with aqueous fullerene C60 dispersion (ADF) and C60-Lys adduct. Methods. The total RNA was extracted from ADF and C60-Lys-stimulated (24 h) human melanoma (Mel Is and Mel Cher lines) and U-937 cells using the RNeasy Mini Kit (Qiagen, Courtaboeuf, France) according to the manufacturer’s instructions. Quantitative real-time PCR analysis of mRNA expression of AHR, NRF2 was performed using iQ5 system (Bio-Rad, USA) and PCRMix kit (Sintol, Russia). Results. Treatment of the cells with ADF and C60-Lys resulted in suppression of AHR mRNA expression by about 50 and 20% for melanoma and U-937 cells, respectively. NRF2 expression was increased 1.5-fold compared to the control group (without treatment).

    Conclusion. We assume that these results indicate that AhR is a very likely target for fullerene C60. Increased NRF2 expression may lead to activation of the NRF2/HO-1 signaling pathway that in turn increases the antioxidant capacity of cells. This effect is directly associated with the anti-inflammatory activity of fullerene C60 described in various studies. Moreover, an association between AHR expression and viral load in infected patients was shown by other authors for some viral infections, and the pharmacological inhibition of AHR suppressed the replication. These data indicate the significant potential of fullerene С60 as a basis for effective antiviral drugs.

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            Авторы номера
            • Автор: Евгения Валерьевна Назарова

              кандидат медицинских наук, заместитель главного врача по клинико-экспертной работе, заведующая отделением госпитализации ФГБУ «ГНЦ Институт иммунологии» ФМБА России.

            • Автор: Оксана Михайловна Курбачева

              профессор, доктор медицинских наук, заведующая отделением бронхиальной астмы ФГБУ «ГНЦ «Институт иммунологии» ФМБА России, профессор кафедры клинической аллергологии и иммунологии лечебного факультета Московского государственного...

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