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Kunitz-Type Peptides from Sea Anemones Protect Neuronal Cells against Parkinson’s Disease Inductors via Inhibition of ROS Production and ATP-Induced P2X7 Receptor Activation
Parkinson’s disease (PD) is a socially significant disease, during the development of which oxidative stress and inflammation play a significant role. Here, we studied the neuroprotective effects of four Kunitz-type peptides from Heteractis crispa and Heteractis magnifica sea anemones against PD ind...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103184/ https://www.ncbi.nlm.nih.gov/pubmed/35563513 http://dx.doi.org/10.3390/ijms23095115 |
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author | Kvetkina, Aleksandra Pislyagin, Evgeny Menchinskaya, Ekaterina Yurchenko, Ekaterina Kalina, Rimma Kozlovskiy, Sergei Kaluzhskiy, Leonid Menshov, Alexander Kim, Natalia Peigneur, Steve Tytgat, Jan Ivanov, Alexis Ayvazyan, Naira Leychenko, Elena Aminin, Dmitry |
author_facet | Kvetkina, Aleksandra Pislyagin, Evgeny Menchinskaya, Ekaterina Yurchenko, Ekaterina Kalina, Rimma Kozlovskiy, Sergei Kaluzhskiy, Leonid Menshov, Alexander Kim, Natalia Peigneur, Steve Tytgat, Jan Ivanov, Alexis Ayvazyan, Naira Leychenko, Elena Aminin, Dmitry |
author_sort | Kvetkina, Aleksandra |
collection | PubMed |
description | Parkinson’s disease (PD) is a socially significant disease, during the development of which oxidative stress and inflammation play a significant role. Here, we studied the neuroprotective effects of four Kunitz-type peptides from Heteractis crispa and Heteractis magnifica sea anemones against PD inductors. The peptide HCIQ1c9, which was obtained for the first time, inhibited trypsin less than other peptides due to unfavorable interactions of Arg17 with Lys43 in the enzyme. Its activity was reduced by up to 70% over the temperature range of 60–100 °C, while HCIQ2c1, HCIQ4c7, and HMIQ3c1 retained their conformation and stayed active up to 90–100 °C. All studied peptides inhibited paraquat- and rotenone-induced intracellular ROS formation, in particular NO, and scavenged free radicals outside the cells. The peptides did not modulate the TRPV1 channels but they affected the P2X7R, both of which are considered therapeutic targets in Parkinson’s disease. HMIQ3c1 and HCIQ4c7 almost completely inhibited the ATP-induced uptake of YO-PRO-1 dye in Neuro-2a cells through P2X7 ion channels and significantly reduced the stable calcium response in these cells. The complex formation of the peptides with the P2X7R extracellular domain was determined via SPR analysis. Thus, these peptides may be considered promising compounds to protect neuronal cells against PD inductors, which act as ROS production inhibitors and partially act as ATP-induced P2X7R activation inhibitors. |
format | Online Article Text |
id | pubmed-9103184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91031842022-05-14 Kunitz-Type Peptides from Sea Anemones Protect Neuronal Cells against Parkinson’s Disease Inductors via Inhibition of ROS Production and ATP-Induced P2X7 Receptor Activation Kvetkina, Aleksandra Pislyagin, Evgeny Menchinskaya, Ekaterina Yurchenko, Ekaterina Kalina, Rimma Kozlovskiy, Sergei Kaluzhskiy, Leonid Menshov, Alexander Kim, Natalia Peigneur, Steve Tytgat, Jan Ivanov, Alexis Ayvazyan, Naira Leychenko, Elena Aminin, Dmitry Int J Mol Sci Article Parkinson’s disease (PD) is a socially significant disease, during the development of which oxidative stress and inflammation play a significant role. Here, we studied the neuroprotective effects of four Kunitz-type peptides from Heteractis crispa and Heteractis magnifica sea anemones against PD inductors. The peptide HCIQ1c9, which was obtained for the first time, inhibited trypsin less than other peptides due to unfavorable interactions of Arg17 with Lys43 in the enzyme. Its activity was reduced by up to 70% over the temperature range of 60–100 °C, while HCIQ2c1, HCIQ4c7, and HMIQ3c1 retained their conformation and stayed active up to 90–100 °C. All studied peptides inhibited paraquat- and rotenone-induced intracellular ROS formation, in particular NO, and scavenged free radicals outside the cells. The peptides did not modulate the TRPV1 channels but they affected the P2X7R, both of which are considered therapeutic targets in Parkinson’s disease. HMIQ3c1 and HCIQ4c7 almost completely inhibited the ATP-induced uptake of YO-PRO-1 dye in Neuro-2a cells through P2X7 ion channels and significantly reduced the stable calcium response in these cells. The complex formation of the peptides with the P2X7R extracellular domain was determined via SPR analysis. Thus, these peptides may be considered promising compounds to protect neuronal cells against PD inductors, which act as ROS production inhibitors and partially act as ATP-induced P2X7R activation inhibitors. MDPI 2022-05-04 /pmc/articles/PMC9103184/ /pubmed/35563513 http://dx.doi.org/10.3390/ijms23095115 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kvetkina, Aleksandra Pislyagin, Evgeny Menchinskaya, Ekaterina Yurchenko, Ekaterina Kalina, Rimma Kozlovskiy, Sergei Kaluzhskiy, Leonid Menshov, Alexander Kim, Natalia Peigneur, Steve Tytgat, Jan Ivanov, Alexis Ayvazyan, Naira Leychenko, Elena Aminin, Dmitry Kunitz-Type Peptides from Sea Anemones Protect Neuronal Cells against Parkinson’s Disease Inductors via Inhibition of ROS Production and ATP-Induced P2X7 Receptor Activation |
title | Kunitz-Type Peptides from Sea Anemones Protect Neuronal Cells against Parkinson’s Disease Inductors via Inhibition of ROS Production and ATP-Induced P2X7 Receptor Activation |
title_full | Kunitz-Type Peptides from Sea Anemones Protect Neuronal Cells against Parkinson’s Disease Inductors via Inhibition of ROS Production and ATP-Induced P2X7 Receptor Activation |
title_fullStr | Kunitz-Type Peptides from Sea Anemones Protect Neuronal Cells against Parkinson’s Disease Inductors via Inhibition of ROS Production and ATP-Induced P2X7 Receptor Activation |
title_full_unstemmed | Kunitz-Type Peptides from Sea Anemones Protect Neuronal Cells against Parkinson’s Disease Inductors via Inhibition of ROS Production and ATP-Induced P2X7 Receptor Activation |
title_short | Kunitz-Type Peptides from Sea Anemones Protect Neuronal Cells against Parkinson’s Disease Inductors via Inhibition of ROS Production and ATP-Induced P2X7 Receptor Activation |
title_sort | kunitz-type peptides from sea anemones protect neuronal cells against parkinson’s disease inductors via inhibition of ros production and atp-induced p2x7 receptor activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103184/ https://www.ncbi.nlm.nih.gov/pubmed/35563513 http://dx.doi.org/10.3390/ijms23095115 |
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