Neurotoxic Effect of Flavonol Myricetin in the Presence of
Excess Copper

J 2021

Neurotoxic Effect of Flavonol Myricetin in the Presence of Excess Copper

SADZAK, Anja, Ignacija VLASIC, Zoran KIRALJ, Marijana BATARELO, Nada ORSOLIC et. al.

Basic information

Original name

Neurotoxic Effect of Flavonol Myricetin in the Presence of Excess Copper

Authors

SADZAK, Anja, Ignacija VLASIC, Zoran KIRALJ, Marijana BATARELO, Nada ORSOLIC, Jazvinscak Jembrek MAJA, Ines KUSEN and Suzana SEGOTA

Edition

Blood Cells, Molecules and Diseases, Orlando, Florida, Academic Press, 2021, 1079-9796

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30103 Neurosciences

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.372

DOI

http://dx.doi.org/10.3390/molecules26040845

UT WoS

000624185500001

Keywords in English

myricetin; prooxidative activity; copper toxicity; atomic force microscopy; elasticity; roughness

Abstract

V originále

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.

Links

90127, large research infrastructures

Name: CIISB II

Citovat

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. 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.

@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.

Detailed Information on Publication Record