‘Trojan-Horse’ stress-granule formation mediated by manganese oxide nanoparticles

Nina B. Illarionova, Ksenia N. Morozova, Dmitry V. Petrovskii, Marina B. Sharapova, Alexander V. Romashchenko, Sergey Y. Troitskii, Elena Kiseleva, Yuri M. Moshkin, Mikhail P. Moshkin

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

Exposure to nanomaterials is considered as one of the risk factors for neurodegenerative pathology. In vitro inorganic nanoparticles (NPs) absorb intrinsically disordered proteins, many of which are the constituents of stress-granules (SGs). SGs normally form in response to cellular stress and, here, we addressed whether selected inorganic NPs could trigger SGs formation in cells. To this end, we have tested a series of inorganic NPs for their ability to induce SGs formation in human glioblastoma and fibroblast cell lines. Among tested NPs, only Mn3O4 NPs triggered SGs formation in cell-type-specific and metabolic-dependent manner. In human glioblastoma U87 MG cell line, Mn3O4 NPs entered cells within minutes and resided inside intracellular vesicles for at least 48 h. Mn3O4 NPs induced a strong reduction in oxidative phosphorylation rate, but not glycolysis. We showed that Mn3O4 NPs slowly dissolve producing a local net of Mn2+ cations, which are known to inhibit oxidative phosphorylation. Indeed, direct incubation of cells with equimolar amounts of Mn2+ cations triggered SGs formation and reduced cellular respiration rate. However, while SGs formed in response to Mn3O4 NPs persisted for hours, SGs formation by Mn2+ peaked and dropped within minutes. Finally, Mn3O4 NPs mediated SGs formation via the phosphorylation of eIF2α. Thus, we conclude that exposure of U87 MG cells to Mn3O4 NPs caused a ‘Trojan-horse’ prolonged SGs response.

Язык оригиналаанглийский
Страницы (с-по)1432-1444
Число страниц13
ЖурналNanotoxicology
Том14
Номер выпуска10
Ранняя дата в режиме онлайн15 дек 2020
DOI
СостояниеОпубликовано - дек 2020

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