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 <i>Heteractis crispa</i> and <i>Heteractis magnifica...
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2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/5115 |
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| author | Aleksandra Kvetkina Evgeny Pislyagin Ekaterina Menchinskaya Ekaterina Yurchenko Rimma Kalina Sergei Kozlovskiy Leonid Kaluzhskiy Alexander Menshov Natalia Kim Steve Peigneur Jan Tytgat Alexis Ivanov Naira Ayvazyan Elena Leychenko Dmitry Aminin |
| author_facet | Aleksandra Kvetkina Evgeny Pislyagin Ekaterina Menchinskaya Ekaterina Yurchenko Rimma Kalina Sergei Kozlovskiy Leonid Kaluzhskiy Alexander Menshov Natalia Kim Steve Peigneur Jan Tytgat Alexis Ivanov Naira Ayvazyan Elena Leychenko Dmitry Aminin |
| author_sort | Aleksandra Kvetkina |
| collection | DOAJ |
| 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 <i>Heteractis crispa</i> and <i>Heteractis magnifica</i> 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. |
| first_indexed | 2024-03-10T04:04:05Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:04:05Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2ea640bccc5c45b1a8230d730b5d0c0c2023-11-23T08:27:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-01239511510.3390/ijms23095115Kunitz-Type Peptides from Sea Anemones Protect Neuronal Cells against Parkinson’s Disease Inductors via Inhibition of ROS Production and ATP-Induced P2X7 Receptor ActivationAleksandra Kvetkina0Evgeny Pislyagin1Ekaterina Menchinskaya2Ekaterina Yurchenko3Rimma Kalina4Sergei Kozlovskiy5Leonid Kaluzhskiy6Alexander Menshov7Natalia Kim8Steve Peigneur9Jan Tytgat10Alexis Ivanov11Naira Ayvazyan12Elena Leychenko13Dmitry Aminin14G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaV.N. Orekhovich Institute of Biomedical Chemistry, 10, Pogodinskaya St., 119121 Moscow, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaToxicology and Pharmacology, Campus Gasthuisberg O&N2, University of Leuven (KU Leuven), Herestraat 49, P.O. Box 922, B-3000 Leuven, BelgiumToxicology and Pharmacology, Campus Gasthuisberg O&N2, University of Leuven (KU Leuven), Herestraat 49, P.O. Box 922, B-3000 Leuven, BelgiumV.N. Orekhovich Institute of Biomedical Chemistry, 10, Pogodinskaya St., 119121 Moscow, RussiaL.A. Orbeli Institute of Physiology, National Academy of Sciences of Armenia, Yerevan 0028, ArmeniaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaParkinson’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 <i>Heteractis crispa</i> and <i>Heteractis magnifica</i> 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.https://www.mdpi.com/1422-0067/23/9/5115Kunitz-type peptidesneuroprotective activitysea anemonesTRPV1P2X7RParkinson’s disease (PD) |
| spellingShingle | Aleksandra Kvetkina Evgeny Pislyagin Ekaterina Menchinskaya Ekaterina Yurchenko Rimma Kalina Sergei Kozlovskiy Leonid Kaluzhskiy Alexander Menshov Natalia Kim Steve Peigneur Jan Tytgat Alexis Ivanov Naira Ayvazyan Elena Leychenko Dmitry Aminin 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 International Journal of Molecular Sciences Kunitz-type peptides neuroprotective activity sea anemones TRPV1 P2X7R Parkinson’s disease (PD) |
| 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 | Kunitz-type peptides neuroprotective activity sea anemones TRPV1 P2X7R Parkinson’s disease (PD) |
| url | https://www.mdpi.com/1422-0067/23/9/5115 |
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