Research output: Contribution to journal › Article › peer-review
‘Trojan-Horse’ stress-granule formation mediated by manganese oxide nanoparticles. / Illarionova, Nina B.; Morozova, Ksenia N.; Petrovskii, Dmitry V. et al.
In: Nanotoxicology, Vol. 14, No. 10, 12.2020, p. 1432-1444.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - ‘Trojan-Horse’ stress-granule formation mediated by manganese oxide nanoparticles
AU - Illarionova, Nina B.
AU - Morozova, Ksenia N.
AU - Petrovskii, Dmitry V.
AU - Sharapova, Marina B.
AU - Romashchenko, Alexander V.
AU - Troitskii, Sergey Y.
AU - Kiseleva, Elena
AU - Moshkin, Yuri M.
AU - Moshkin, Mikhail P.
N1 - Publisher Copyright: © 2020 Informa UK Limited, trading as Taylor & Francis Group. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - manganese oxide
KW - Nanoparticles
KW - oxidative phosphorylation
KW - stress-granules
KW - Trojan-Horse mechanism
KW - RNA GRANULES
KW - OXIDATIVE STRESS
KW - MITOCHONDRIA
KW - TOXICITY
KW - IRON
KW - CELLULAR UPTAKE
KW - CYTOTOXICITY
KW - MN2+
UR - http://www.scopus.com/inward/record.url?scp=85097567432&partnerID=8YFLogxK
U2 - 10.1080/17435390.2020.1856433
DO - 10.1080/17435390.2020.1856433
M3 - Article
C2 - 33320703
AN - SCOPUS:85097567432
VL - 14
SP - 1432
EP - 1444
JO - Nanotoxicology
JF - Nanotoxicology
SN - 1743-5390
IS - 10
ER -
ID: 27086054