Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 Cells

Sulforaphane (SFN) is a naturally occurring isothiocyanate that is abundant in many cruciferous vegetables, such as broccoli and cauliflower, and it has been observed to exert numerous biological activities. In the present study, we investigate the effect of SFN on eNOS, a key regulatory enzyme of v...

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Main Authors: Ying Zhang, Pham Ngoc Khoi, Bangrong Cai, Dhiraj Kumar Sah, Young-Do Jung
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/17/5422
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author Ying Zhang
Pham Ngoc Khoi
Bangrong Cai
Dhiraj Kumar Sah
Young-Do Jung
author_facet Ying Zhang
Pham Ngoc Khoi
Bangrong Cai
Dhiraj Kumar Sah
Young-Do Jung
author_sort Ying Zhang
collection DOAJ
description Sulforaphane (SFN) is a naturally occurring isothiocyanate that is abundant in many cruciferous vegetables, such as broccoli and cauliflower, and it has been observed to exert numerous biological activities. In the present study, we investigate the effect of SFN on eNOS, a key regulatory enzyme of vascular homeostasis and underlying intracellular pathways, in human endothelial EA.hy926 cells. The results indicate that SFN treatment significantly increases NO production and eNOS phosphorylation in a time- and dose-dependent fashion and also augments Akt phosphorylation in a time- and dose-dependent manner. Meanwhile, pretreatment with LY294002 (a specific PI3K inhibitor) suppresses the phosphorylation of eNOS and NO production. Furthermore, SFN time- and dose-dependently induces the phosphorylation of Src kinase, a further upstream regulator of PI3K, while PP2 pretreatment (a specific Src inhibitor) eliminates the increase in phosphorylated Akt, eNOS and the production of NO derived from eNOS. Overall, the present study uncovers a novel effect of SFN to stimulate eNOS activity in EA.hy926 cells by regulating NO bioavailability. These findings provide clear evidence that SFN regulates eNOS activity and NO bioavailability, suggesting a promising therapeutic candidate to prevent endothelial dysfunction, atherosclerosis and other cardiovascular diseases.
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spelling doaj.art-5d451f24fdc84e1bb8083a8323d4d01b2023-11-23T13:41:42ZengMDPI AGMolecules1420-30492022-08-012717542210.3390/molecules27175422Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 CellsYing Zhang0Pham Ngoc Khoi1Bangrong Cai2Dhiraj Kumar Sah3Young-Do Jung4Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang 212013, ChinaResearch Institute of Biomedical Sciences, Chonnam National University Medical School, Gwangju 501-190, KoreaSchool of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, ChinaResearch Institute of Biomedical Sciences, Chonnam National University Medical School, Gwangju 501-190, KoreaResearch Institute of Biomedical Sciences, Chonnam National University Medical School, Gwangju 501-190, KoreaSulforaphane (SFN) is a naturally occurring isothiocyanate that is abundant in many cruciferous vegetables, such as broccoli and cauliflower, and it has been observed to exert numerous biological activities. In the present study, we investigate the effect of SFN on eNOS, a key regulatory enzyme of vascular homeostasis and underlying intracellular pathways, in human endothelial EA.hy926 cells. The results indicate that SFN treatment significantly increases NO production and eNOS phosphorylation in a time- and dose-dependent fashion and also augments Akt phosphorylation in a time- and dose-dependent manner. Meanwhile, pretreatment with LY294002 (a specific PI3K inhibitor) suppresses the phosphorylation of eNOS and NO production. Furthermore, SFN time- and dose-dependently induces the phosphorylation of Src kinase, a further upstream regulator of PI3K, while PP2 pretreatment (a specific Src inhibitor) eliminates the increase in phosphorylated Akt, eNOS and the production of NO derived from eNOS. Overall, the present study uncovers a novel effect of SFN to stimulate eNOS activity in EA.hy926 cells by regulating NO bioavailability. These findings provide clear evidence that SFN regulates eNOS activity and NO bioavailability, suggesting a promising therapeutic candidate to prevent endothelial dysfunction, atherosclerosis and other cardiovascular diseases.https://www.mdpi.com/1420-3049/27/17/5422sulforaphaneSrcAkteNOSNOEA.hy926
spellingShingle Ying Zhang
Pham Ngoc Khoi
Bangrong Cai
Dhiraj Kumar Sah
Young-Do Jung
Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 Cells
Molecules
sulforaphane
Src
Akt
eNOS
NO
EA.hy926
title Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 Cells
title_full Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 Cells
title_fullStr Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 Cells
title_full_unstemmed Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 Cells
title_short Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 Cells
title_sort sulforaphane regulates enos activation and no production via src mediated pi3k akt signaling in human endothelial ea hy926 cells
topic sulforaphane
Src
Akt
eNOS
NO
EA.hy926
url https://www.mdpi.com/1420-3049/27/17/5422
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