Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity
Recently, manipulations with reactive astrocytes have been viewed as a new therapeutic approach that will enable the development of treatments for acute brain injuries and neurodegenerative diseases. Astrocytes can release several substances, which may exert neurotoxic or neuroprotective effects, bu...
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2021-07-01
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| Online Access: | https://www.mdpi.com/2218-1989/11/8/498 |
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| author | Mariia V. Guryleva Dmitry V. Chistyakov Alexander V. Lopachev Sergei V. Goriainov Alina A. Astakhova Yulia A. Timoshina Anastasiya V. Khutorova Tatiana N. Fedorova Marina G. Sergeeva |
| author_facet | Mariia V. Guryleva Dmitry V. Chistyakov Alexander V. Lopachev Sergei V. Goriainov Alina A. Astakhova Yulia A. Timoshina Anastasiya V. Khutorova Tatiana N. Fedorova Marina G. Sergeeva |
| author_sort | Mariia V. Guryleva |
| collection | DOAJ |
| description | Recently, manipulations with reactive astrocytes have been viewed as a new therapeutic approach that will enable the development of treatments for acute brain injuries and neurodegenerative diseases. Astrocytes can release several substances, which may exert neurotoxic or neuroprotective effects, but the nature of these substances is still largely unknown. In the present work, we tested the hypothesis that these effects may be attributed to oxylipins, which are synthesized from n-3 or n-6 polyunsaturated fatty acids (PUFAs). We used astrocyte-enriched cultures and found that: (1) lipid fractions secreted by lipopolysaccharide (LPS)—stimulated rat primary astrocyte-enriched cultures—possessed neurotoxic activity in rat primary neuronal cultures; (2) both of the tested oxylipin synthesis inhibitors, ML355 and Zileuton, reduce the LPS-stimulated release of interleukin 6 (IL-6) by astrocyte cultures, but only ML355 can change lipid fractions from neurotoxic to non-toxic; and (3) oxylipin profiles, measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) from neurotoxic and non-toxic lipid fractions, reveal a group of n-3 docosahexaenoic acid derivatives, hydroxydocosahexaenoic acids (HdoHEs)-4-HdoHE, 8-HdoHE, and 17-HdoHE, which may reflect the neuroprotective features of lipid fractions. Regulating the composition of astrocyte oxylipin profiles may be suggested as an approach for regulation of neurotoxicity in inflammatory processes. |
| first_indexed | 2024-03-10T08:36:34Z |
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| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T08:36:34Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-e14a9d2c1ccd4282a1b059e67a724fef2023-11-22T08:39:10ZengMDPI AGMetabolites2218-19892021-07-0111849810.3390/metabo11080498Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces NeurotoxicityMariia V. Guryleva0Dmitry V. Chistyakov1Alexander V. Lopachev2Sergei V. Goriainov3Alina A. Astakhova4Yulia A. Timoshina5Anastasiya V. Khutorova6Tatiana N. Fedorova7Marina G. Sergeeva8Faculty of Bioengineering and Bioinformatics, Moscow Lomonosov State University, 119234 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaLaboratory of Clinical and Experimental Neurochemistry, Research Center of Neurology, 125367 Moscow, RussiaSREC PFUR, Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaLaboratory of Clinical and Experimental Neurochemistry, Research Center of Neurology, 125367 Moscow, RussiaLaboratory of Clinical and Experimental Neurochemistry, Research Center of Neurology, 125367 Moscow, RussiaLaboratory of Clinical and Experimental Neurochemistry, Research Center of Neurology, 125367 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaRecently, manipulations with reactive astrocytes have been viewed as a new therapeutic approach that will enable the development of treatments for acute brain injuries and neurodegenerative diseases. Astrocytes can release several substances, which may exert neurotoxic or neuroprotective effects, but the nature of these substances is still largely unknown. In the present work, we tested the hypothesis that these effects may be attributed to oxylipins, which are synthesized from n-3 or n-6 polyunsaturated fatty acids (PUFAs). We used astrocyte-enriched cultures and found that: (1) lipid fractions secreted by lipopolysaccharide (LPS)—stimulated rat primary astrocyte-enriched cultures—possessed neurotoxic activity in rat primary neuronal cultures; (2) both of the tested oxylipin synthesis inhibitors, ML355 and Zileuton, reduce the LPS-stimulated release of interleukin 6 (IL-6) by astrocyte cultures, but only ML355 can change lipid fractions from neurotoxic to non-toxic; and (3) oxylipin profiles, measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) from neurotoxic and non-toxic lipid fractions, reveal a group of n-3 docosahexaenoic acid derivatives, hydroxydocosahexaenoic acids (HdoHEs)-4-HdoHE, 8-HdoHE, and 17-HdoHE, which may reflect the neuroprotective features of lipid fractions. Regulating the composition of astrocyte oxylipin profiles may be suggested as an approach for regulation of neurotoxicity in inflammatory processes.https://www.mdpi.com/2218-1989/11/8/498astrocytesneuronsML355Zileutonlipoxygenasesinterleukin 10 (IL-10) |
| spellingShingle | Mariia V. Guryleva Dmitry V. Chistyakov Alexander V. Lopachev Sergei V. Goriainov Alina A. Astakhova Yulia A. Timoshina Anastasiya V. Khutorova Tatiana N. Fedorova Marina G. Sergeeva Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity Metabolites astrocytes neurons ML355 Zileuton lipoxygenases interleukin 10 (IL-10) |
| title | Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity |
| title_full | Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity |
| title_fullStr | Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity |
| title_full_unstemmed | Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity |
| title_short | Modulation of the Primary Astrocyte-Enriched Cultures’ Oxylipin Profiles Reduces Neurotoxicity |
| title_sort | modulation of the primary astrocyte enriched cultures oxylipin profiles reduces neurotoxicity |
| topic | astrocytes neurons ML355 Zileuton lipoxygenases interleukin 10 (IL-10) |
| url | https://www.mdpi.com/2218-1989/11/8/498 |
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