Targeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR55

Oxidative stress is associated with different neurological and psychiatric diseases. Therefore, development of new pharmaceuticals targeting oxidative dysregulation might be a promising approach to treat these diseases. The G-protein coupled receptor 55 (GPR55) is broadly expressed in central nervou...

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Autores principales:	Matthias Apweiler, Soraya Wilke Saliba, Jana Streyczek, Thomas Hurrle, Simone Gräßle, Stefan Bräse, Bernd L. Fiebich
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	oxidative stress GPR55 coumarin-based compounds ROS inverse agonism 8-Iso-PGF<sub>2α</sub> Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/53573912c7d940c28090b1526114831b
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spelling	oai:doaj.org-article:53573912c7d940c28090b1526114831b2021-11-11T17:07:53ZTargeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR5510.3390/ijms2221116651422-00671661-6596https://doaj.org/article/53573912c7d940c28090b1526114831b2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11665https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Oxidative stress is associated with different neurological and psychiatric diseases. Therefore, development of new pharmaceuticals targeting oxidative dysregulation might be a promising approach to treat these diseases. The G-protein coupled receptor 55 (GPR55) is broadly expressed in central nervous tissues and cells and is involved in the regulation of inflammatory and oxidative cell homeostasis. We have recently shown that coumarin-based compounds enfold inverse agonistic activities at GPR55 resulting in the inhibition of prostaglandin E<sub>2</sub>. However, the antioxidative effects mediated by GPR55 were not evaluated yet. Therefore, we investigated the antioxidative effects of two novel synthesized coumarin-based compounds, KIT C and KIT H, in primary mouse microglial and human neuronal SK-N-SK cells. KIT C and KIT H show antioxidative properties in SK-N-SH cells as well as in primary microglia. In GPR55-knockout SK-N-SH cells, the antioxidative effects are abolished, suggesting a GPR55-dependent antioxidative mechanism. Since inverse agonistic GPR55 activation in the brain seems to be associated with decreased oxidative stress, KIT C and KIT H possibly act as inverse agonists of GPR55 eliciting promising therapeutic options for oxidative stress related diseases.Matthias ApweilerSoraya Wilke SalibaJana StreyczekThomas HurrleSimone GräßleStefan BräseBernd L. FiebichMDPI AGarticleoxidative stressGPR55coumarin-based compoundsROSinverse agonism8-Iso-PGF<sub>2α</sub>Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11665, p 11665 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oxidative stress GPR55 coumarin-based compounds ROS inverse agonism 8-Iso-PGF<sub>2α</sub> Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	oxidative stress GPR55 coumarin-based compounds ROS inverse agonism 8-Iso-PGF<sub>2α</sub> Biology (General) QH301-705.5 Chemistry QD1-999 Matthias Apweiler Soraya Wilke Saliba Jana Streyczek Thomas Hurrle Simone Gräßle Stefan Bräse Bernd L. Fiebich Targeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR55
description	Oxidative stress is associated with different neurological and psychiatric diseases. Therefore, development of new pharmaceuticals targeting oxidative dysregulation might be a promising approach to treat these diseases. The G-protein coupled receptor 55 (GPR55) is broadly expressed in central nervous tissues and cells and is involved in the regulation of inflammatory and oxidative cell homeostasis. We have recently shown that coumarin-based compounds enfold inverse agonistic activities at GPR55 resulting in the inhibition of prostaglandin E<sub>2</sub>. However, the antioxidative effects mediated by GPR55 were not evaluated yet. Therefore, we investigated the antioxidative effects of two novel synthesized coumarin-based compounds, KIT C and KIT H, in primary mouse microglial and human neuronal SK-N-SK cells. KIT C and KIT H show antioxidative properties in SK-N-SH cells as well as in primary microglia. In GPR55-knockout SK-N-SH cells, the antioxidative effects are abolished, suggesting a GPR55-dependent antioxidative mechanism. Since inverse agonistic GPR55 activation in the brain seems to be associated with decreased oxidative stress, KIT C and KIT H possibly act as inverse agonists of GPR55 eliciting promising therapeutic options for oxidative stress related diseases.
format	article
author	Matthias Apweiler Soraya Wilke Saliba Jana Streyczek Thomas Hurrle Simone Gräßle Stefan Bräse Bernd L. Fiebich
author_facet	Matthias Apweiler Soraya Wilke Saliba Jana Streyczek Thomas Hurrle Simone Gräßle Stefan Bräse Bernd L. Fiebich
author_sort	Matthias Apweiler
title	Targeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR55
title_short	Targeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR55
title_full	Targeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR55
title_fullStr	Targeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR55
title_full_unstemmed	Targeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR55
title_sort	targeting oxidative stress: novel coumarin-based inverse agonists of gpr55
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/53573912c7d940c28090b1526114831b
work_keys_str_mv	AT matthiasapweiler targetingoxidativestressnovelcoumarinbasedinverseagonistsofgpr55 AT sorayawilkesaliba targetingoxidativestressnovelcoumarinbasedinverseagonistsofgpr55 AT janastreyczek targetingoxidativestressnovelcoumarinbasedinverseagonistsofgpr55 AT thomashurrle targetingoxidativestressnovelcoumarinbasedinverseagonistsofgpr55 AT simonegraßle targetingoxidativestressnovelcoumarinbasedinverseagonistsofgpr55 AT stefanbrase targetingoxidativestressnovelcoumarinbasedinverseagonistsofgpr55 AT berndlfiebich targetingoxidativestressnovelcoumarinbasedinverseagonistsofgpr55
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Targeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR55

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