The toxic effect of Cu2+ on cultured astrocytes of the rat cerebral cortex is associated with the nucleolar stress

Isaev, N.K.; Genrikhs, E.E.; Smirnova, E.A.; Wang, W.; Lapieva, A.E.; Golyshev, S.A.; Voronkov, D.N.; Strizhkova, A.B.; Berdnikov, A.K.; Stelmashook, E.V.

Авторы: Isaev Nickolay K., Genrikhs Elizaveta E., Smirnova Elena A., Wang Wenzhu, Lapieva Alina E., Golyshev Sergey A., Voronkov Dmitry N., Strizhkova Anna B., Berdnikov Arseniy K., Stelmashook Elena V.
Журнал: Journal of Trace Elements in Medicine and Biology
Том: 93
Год издания: 2026
Издательство: Elsevier BV
Местоположение издательства: Netherlands
Номер статьи: 127821
DOI: 10.1016/j.jtemb.2026.127821
Аннотация: Copper-induced cell death (cuproptosis) is implicated in the pathogenesis of Wilson's disease, there-fore it is important to understand how copper ions can affect brain astrocytes, as these cells play an important role in copper metabolism. The cultured astrocytes were incubated with various concentra-tions of CuCl2 (0.025–0.2 mM) for 24 h. CuCl2 caused dose-dependent decrease in cell viability. Statistically significant decrease in cell viability (85 %) was detected at 0.05 mM Cu2+ . Higher con-centrations of copper (0.1 mM and 0.2 mM) reduced cell viability to 80 % and 59 %, respectively. The concentration 0.1 mM was used for further experiments. In the surviving cells treated with 24 h Cu2+ , there was a significant increase in the level of the p53 protein and changes in the localization of nucleophosmin/B23 in nuclei of cultured astrocytes, increase in the size of the nucleoli to 2.47 ± 0.1 µm2 compared to 1.35 ± 0.04 µm2 in the control and a decrease in the mitochondrial membrane potential. The electron microscopy showed that copper induced a redistribution of the dense fibrillar component to the nucleolar periphery and a disorganization of the whole nucleolar structure. Our results show that the nucleoli are one of the main targets of Cu-induced damage, leading to the development of nucleolar stress.
Добавил в систему: Исаев Николай Константинович

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