Cannabidiol induces autophagy via ERK1/2 activation in neural cells

Abstract Autophagy is a lysosomal catabolic process essential to cell homeostasis and is related to the neuroprotection of the central nervous system. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid present in Cannabis sativa. Many therapeutic actions have been linked to this compound, incl...

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Autores principales:	Talita A. M. Vrechi, Anderson H. F. F. Leão, Ingrid B. M. Morais, Vanessa C. Abílio, Antonio W. Zuardi, Jaime Eduardo C. Hallak, José Alexandre Crippa, Claudia Bincoletto, Rodrigo P. Ureshino, Soraya S. Smaili, Gustavo J. S. Pereira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a46c941a43f34917aeb73fb065d339df
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spelling	oai:doaj.org-article:a46c941a43f34917aeb73fb065d339df2021-12-02T13:35:03ZCannabidiol induces autophagy via ERK1/2 activation in neural cells10.1038/s41598-021-84879-22045-2322https://doaj.org/article/a46c941a43f34917aeb73fb065d339df2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84879-2https://doaj.org/toc/2045-2322Abstract Autophagy is a lysosomal catabolic process essential to cell homeostasis and is related to the neuroprotection of the central nervous system. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid present in Cannabis sativa. Many therapeutic actions have been linked to this compound, including autophagy activation. However, the precise underlying molecular mechanisms remain unclear, and the downstream functional significance of these actions has yet to be determined. Here, we investigated CBD-evoked effects on autophagy in human neuroblastoma SH-SY5Y and murine astrocyte cell lines. We found that CBD-induced autophagy was substantially reduced in the presence of CB1, CB2 and TRPV1 receptor antagonists, AM 251, AM 630 and capsazepine, respectively. This result strongly indicates that the activation of these receptors mediates the autophagic flux. Additionally, we demonstrated that CBD activates autophagy through ERK1/2 activation and AKT suppression. Interestingly, CBD-mediated autophagy activation is dependent on the autophagy initiator ULK1, but mTORC1 independent. Thus, it is plausible that a non-canonical pathway is involved. Our findings collectively provide evidence that CBD stimulates autophagy signal transduction via crosstalk between the ERK1/2 and AKT kinases, which represent putative regulators of cell proliferation and survival. Furthermore, our study sheds light on potential therapeutic cannabinoid targets that could be developed for treating neurodegenerative disorders.Talita A. M. VrechiAnderson H. F. F. LeãoIngrid B. M. MoraisVanessa C. AbílioAntonio W. ZuardiJaime Eduardo C. HallakJosé Alexandre CrippaClaudia BincolettoRodrigo P. UreshinoSoraya S. SmailiGustavo J. S. PereiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Talita A. M. Vrechi Anderson H. F. F. Leão Ingrid B. M. Morais Vanessa C. Abílio Antonio W. Zuardi Jaime Eduardo C. Hallak José Alexandre Crippa Claudia Bincoletto Rodrigo P. Ureshino Soraya S. Smaili Gustavo J. S. Pereira Cannabidiol induces autophagy via ERK1/2 activation in neural cells
description	Abstract Autophagy is a lysosomal catabolic process essential to cell homeostasis and is related to the neuroprotection of the central nervous system. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid present in Cannabis sativa. Many therapeutic actions have been linked to this compound, including autophagy activation. However, the precise underlying molecular mechanisms remain unclear, and the downstream functional significance of these actions has yet to be determined. Here, we investigated CBD-evoked effects on autophagy in human neuroblastoma SH-SY5Y and murine astrocyte cell lines. We found that CBD-induced autophagy was substantially reduced in the presence of CB1, CB2 and TRPV1 receptor antagonists, AM 251, AM 630 and capsazepine, respectively. This result strongly indicates that the activation of these receptors mediates the autophagic flux. Additionally, we demonstrated that CBD activates autophagy through ERK1/2 activation and AKT suppression. Interestingly, CBD-mediated autophagy activation is dependent on the autophagy initiator ULK1, but mTORC1 independent. Thus, it is plausible that a non-canonical pathway is involved. Our findings collectively provide evidence that CBD stimulates autophagy signal transduction via crosstalk between the ERK1/2 and AKT kinases, which represent putative regulators of cell proliferation and survival. Furthermore, our study sheds light on potential therapeutic cannabinoid targets that could be developed for treating neurodegenerative disorders.
format	article
author	Talita A. M. Vrechi Anderson H. F. F. Leão Ingrid B. M. Morais Vanessa C. Abílio Antonio W. Zuardi Jaime Eduardo C. Hallak José Alexandre Crippa Claudia Bincoletto Rodrigo P. Ureshino Soraya S. Smaili Gustavo J. S. Pereira
author_facet	Talita A. M. Vrechi Anderson H. F. F. Leão Ingrid B. M. Morais Vanessa C. Abílio Antonio W. Zuardi Jaime Eduardo C. Hallak José Alexandre Crippa Claudia Bincoletto Rodrigo P. Ureshino Soraya S. Smaili Gustavo J. S. Pereira
author_sort	Talita A. M. Vrechi
title	Cannabidiol induces autophagy via ERK1/2 activation in neural cells
title_short	Cannabidiol induces autophagy via ERK1/2 activation in neural cells
title_full	Cannabidiol induces autophagy via ERK1/2 activation in neural cells
title_fullStr	Cannabidiol induces autophagy via ERK1/2 activation in neural cells
title_full_unstemmed	Cannabidiol induces autophagy via ERK1/2 activation in neural cells
title_sort	cannabidiol induces autophagy via erk1/2 activation in neural cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a46c941a43f34917aeb73fb065d339df
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Cannabidiol induces autophagy via ERK1/2 activation in neural cells

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