Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351

Abstract Curcumin, a phytochemical extracted from Curcuma longa rhizomes, is known to be protective in neurons via activation of Nrf2, a master regulator of endogenous defense against oxidative stress in cells. However, the exact mechanism by which curcumin activates Nrf2 remains controversial. Here...

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Autores principales:	Jee-Yun Park, Hee-Young Sohn, Young Ho Koh, Chulman Jo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b97934da2cec41ec9c87cd0077eb6ec0
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spelling	oai:doaj.org-article:b97934da2cec41ec9c87cd0077eb6ec02021-12-02T13:39:29ZCurcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser35110.1038/s41598-021-87225-82045-2322https://doaj.org/article/b97934da2cec41ec9c87cd0077eb6ec02021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87225-8https://doaj.org/toc/2045-2322Abstract Curcumin, a phytochemical extracted from Curcuma longa rhizomes, is known to be protective in neurons via activation of Nrf2, a master regulator of endogenous defense against oxidative stress in cells. However, the exact mechanism by which curcumin activates Nrf2 remains controversial. Here, we observed that curcumin induced the expression of genes downstream of Nrf2 such as HO-1, NQO1, and GST-mu1 in neuronal cells, and increased the level of Nrf2 protein. Notably, the level of p62 phosphorylation at S351 (S349 in human) was significantly increased in cells treated with curcumin. Additionally, curcumin-induced Nrf2 activation was abrogated in p62 knockout (−/−) MEFs, indicating that p62 phosphorylation at S351 played a crucial role in curcumin-induced Nrf2 activation. Among the kinases involved in p62 phosphorylation at S351, PKCδ was activated in curcumin-treated cells. The phosphorylation of p62 at S351 was enhanced by transfection of PKCδ expression plasmid; in contrast, it was inhibited in cells treated with PKCδ-specific siRNA. Together, these results suggest that PKCδ is mainly involved in curcumin-induced p62 phosphorylation and Nrf2 activation. Accordingly, we demonstrate for the first time that curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at S351.Jee-Yun ParkHee-Young SohnYoung Ho KohChulman JoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jee-Yun Park Hee-Young Sohn Young Ho Koh Chulman Jo Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351
description	Abstract Curcumin, a phytochemical extracted from Curcuma longa rhizomes, is known to be protective in neurons via activation of Nrf2, a master regulator of endogenous defense against oxidative stress in cells. However, the exact mechanism by which curcumin activates Nrf2 remains controversial. Here, we observed that curcumin induced the expression of genes downstream of Nrf2 such as HO-1, NQO1, and GST-mu1 in neuronal cells, and increased the level of Nrf2 protein. Notably, the level of p62 phosphorylation at S351 (S349 in human) was significantly increased in cells treated with curcumin. Additionally, curcumin-induced Nrf2 activation was abrogated in p62 knockout (−/−) MEFs, indicating that p62 phosphorylation at S351 played a crucial role in curcumin-induced Nrf2 activation. Among the kinases involved in p62 phosphorylation at S351, PKCδ was activated in curcumin-treated cells. The phosphorylation of p62 at S351 was enhanced by transfection of PKCδ expression plasmid; in contrast, it was inhibited in cells treated with PKCδ-specific siRNA. Together, these results suggest that PKCδ is mainly involved in curcumin-induced p62 phosphorylation and Nrf2 activation. Accordingly, we demonstrate for the first time that curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at S351.
format	article
author	Jee-Yun Park Hee-Young Sohn Young Ho Koh Chulman Jo
author_facet	Jee-Yun Park Hee-Young Sohn Young Ho Koh Chulman Jo
author_sort	Jee-Yun Park
title	Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351
title_short	Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351
title_full	Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351
title_fullStr	Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351
title_full_unstemmed	Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351
title_sort	curcumin activates nrf2 through pkcδ-mediated p62 phosphorylation at ser351
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b97934da2cec41ec9c87cd0077eb6ec0
work_keys_str_mv	AT jeeyunpark curcuminactivatesnrf2throughpkcdmediatedp62phosphorylationatser351 AT heeyoungsohn curcuminactivatesnrf2throughpkcdmediatedp62phosphorylationatser351 AT younghokoh curcuminactivatesnrf2throughpkcdmediatedp62phosphorylationatser351 AT chulmanjo curcuminactivatesnrf2throughpkcdmediatedp62phosphorylationatser351
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Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351

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