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@article{2409868,
author = {Sadzak, Anja and Vlasic, Ignacija and Kiralj, Zoran and Batarelo, Marijana and Orsolic, Nada and Maja, Jazvinscak Jembrek and Kusen, Ines and Segota, Suzana},
article_location = {Orlando, Florida},
article_number = {4},
doi = {http://dx.doi.org/10.3390/molecules26040845},
keywords = {myricetin; prooxidative activity; copper toxicity; atomic force microscopy; elasticity; roughness},
language = {eng},
issn = {1079-9796},
journal = {Blood Cells, Molecules and Diseases},
title = {Neurotoxic Effect of Flavonol Myricetin in the Presence of Excess Copper},
url = {https://www.mdpi.com/1420-3049/26/4/845},
volume = {26},
year = {2021}
}
TY - JOUR
ID - 2409868
AU - Sadzak, Anja - Vlasic, Ignacija - Kiralj, Zoran - Batarelo, Marijana - Orsolic, Nada - Maja, Jazvinscak Jembrek - Kusen, Ines - Segota, Suzana
PY - 2021
TI - Neurotoxic Effect of Flavonol Myricetin in the Presence of Excess Copper
JF - Blood Cells, Molecules and Diseases
VL - 26
IS - 4
SP - 1-28
EP - 1-28
PB - Academic Press
SN - 10799796
KW - myricetin
KW - prooxidative activity
KW - copper toxicity
KW - atomic force microscopy
KW - elasticity
KW - roughness
UR - https://www.mdpi.com/1420-3049/26/4/845
N2 - Oxidative stress (OS) induced by the disturbed homeostasis of metal ions is one of the pivotal factors contributing to neurodegeneration. The aim of the present study was to investigate the effects of flavonoid myricetin on copper-induced toxicity in neuroblastoma SH-SY5Y cells. As determined by the MTT method, trypan blue exclusion assay and measurement of ATP production, myricetin heightened the toxic effects of copper and exacerbated cell death. It also increased copper-induced generation of reactive oxygen species, indicating the prooxidative nature of its action. Furthermore, myricetin provoked chromatin condensation and loss of membrane integrity without caspase-3 activation, suggesting the activation of both caspase-independent programmed cell death and necrosis. At the protein level, myricetin-induced upregulation of PARP-1 and decreased expression of Bcl-2, whereas copper-induced changes in the expression of p53, p73, Bax and NME1 were not further affected by myricetin. Inhibitors of ERK1/2 and JNK kinases, protein kinase A and L-type calcium channels exacerbated the toxic effects of myricetin, indicating the involvement of intracellular signaling pathways in cell death. We also employed atomic force microscopy (AFM) to evaluate the morphological and mechanical properties of SH-SY5Y cells at the nanoscale. Consistent with the cellular and molecular methods, this biophysical approach also revealed a myricetin-induced increase in cell surface roughness and reduced elasticity. Taken together, we demonstrated the adverse effects of myricetin, pointing out that caution is required when considering powerful antioxidants for adjuvant therapy in copper-related neurodegeneration.
ER -
SADZAK, Anja, Ignacija VLASIC, Zoran KIRALJ, Marijana BATARELO, Nada ORSOLIC, Jazvinscak Jembrek MAJA, Ines KUSEN and Suzana SEGOTA. Neurotoxic Effect of Flavonol Myricetin in the Presence of Excess Copper. \textit{Blood Cells, Molecules and Diseases}. Orlando, Florida: Academic Press, 2021, vol.~26, No~4, p.~1-28. ISSN~1079-9796. Available from: https://dx.doi.org/10.3390/molecules26040845.
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