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Honokiol ameliorates angiotensin II‐induced hypertension and endothelial dysfunction by inhibiting HDAC6‐mediated cystathionine γ‐lyase degradation
Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (H(2)S) produced by cystathionine γ‐lyase (CSE) promotes vascular relaxation and lowers hypertension. Honokiol (HNK), a natural compound in the Magnolia plant, has been shown to retain mul...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521302/ https://www.ncbi.nlm.nih.gov/pubmed/32755037 http://dx.doi.org/10.1111/jcmm.15686 |
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author | Chi, Zhexi Le, Truc Phan Hoang Lee, Sang Ki Guo, Erling Kim, Dongsoo Lee, Sanha Seo, Seung‐Yong Lee, Sook Young Kim, Jae Hyung Lee, Sang Yoon |
author_facet | Chi, Zhexi Le, Truc Phan Hoang Lee, Sang Ki Guo, Erling Kim, Dongsoo Lee, Sanha Seo, Seung‐Yong Lee, Sook Young Kim, Jae Hyung Lee, Sang Yoon |
author_sort | Chi, Zhexi |
collection | PubMed |
description | Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (H(2)S) produced by cystathionine γ‐lyase (CSE) promotes vascular relaxation and lowers hypertension. Honokiol (HNK), a natural compound in the Magnolia plant, has been shown to retain multifunctional properties such as anti‐oxidative and anti‐inflammatory activities. However, a potential role of HNK in regulating CSE and hypertension remains largely unknown. Here, we aimed to demonstrate that HNK co‐treatment attenuated the vasoconstriction, hypertension and H(2)S reduction caused by angiotensin II (AngII), a well‐established inducer of hypertension. We previously found that histone deacetylase 6 (HDAC6) mediates AngII‐induced deacetylation of CSE, which facilitates its ubiquitination and proteasomal degradation. Our current results indicated that HNK increased endothelial CSE protein levels by enhancing its stability in a sirtuin‐3‐independent manner. Notably, HNK could increase CSE acetylation levels by inhibiting HDAC6 catalytic activity, thereby blocking the AngII‐induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination occurred mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was resistant to both acetylation and ubiquitination, exhibiting higher protein stability than that of wild‐type CSE. Collectively, our findings suggested that HNK treatment protects CSE against HDAC6‐mediated degradation and may constitute an alternative for preventing endothelial dysfunction and hypertensive disorders. |
format | Online Article Text |
id | pubmed-7521302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75213022020-10-02 Honokiol ameliorates angiotensin II‐induced hypertension and endothelial dysfunction by inhibiting HDAC6‐mediated cystathionine γ‐lyase degradation Chi, Zhexi Le, Truc Phan Hoang Lee, Sang Ki Guo, Erling Kim, Dongsoo Lee, Sanha Seo, Seung‐Yong Lee, Sook Young Kim, Jae Hyung Lee, Sang Yoon J Cell Mol Med Original Articles Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (H(2)S) produced by cystathionine γ‐lyase (CSE) promotes vascular relaxation and lowers hypertension. Honokiol (HNK), a natural compound in the Magnolia plant, has been shown to retain multifunctional properties such as anti‐oxidative and anti‐inflammatory activities. However, a potential role of HNK in regulating CSE and hypertension remains largely unknown. Here, we aimed to demonstrate that HNK co‐treatment attenuated the vasoconstriction, hypertension and H(2)S reduction caused by angiotensin II (AngII), a well‐established inducer of hypertension. We previously found that histone deacetylase 6 (HDAC6) mediates AngII‐induced deacetylation of CSE, which facilitates its ubiquitination and proteasomal degradation. Our current results indicated that HNK increased endothelial CSE protein levels by enhancing its stability in a sirtuin‐3‐independent manner. Notably, HNK could increase CSE acetylation levels by inhibiting HDAC6 catalytic activity, thereby blocking the AngII‐induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination occurred mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was resistant to both acetylation and ubiquitination, exhibiting higher protein stability than that of wild‐type CSE. Collectively, our findings suggested that HNK treatment protects CSE against HDAC6‐mediated degradation and may constitute an alternative for preventing endothelial dysfunction and hypertensive disorders. John Wiley and Sons Inc. 2020-08-04 2020-09 /pmc/articles/PMC7521302/ /pubmed/32755037 http://dx.doi.org/10.1111/jcmm.15686 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Chi, Zhexi Le, Truc Phan Hoang Lee, Sang Ki Guo, Erling Kim, Dongsoo Lee, Sanha Seo, Seung‐Yong Lee, Sook Young Kim, Jae Hyung Lee, Sang Yoon Honokiol ameliorates angiotensin II‐induced hypertension and endothelial dysfunction by inhibiting HDAC6‐mediated cystathionine γ‐lyase degradation |
title | Honokiol ameliorates angiotensin II‐induced hypertension and endothelial dysfunction by inhibiting HDAC6‐mediated cystathionine γ‐lyase degradation |
title_full | Honokiol ameliorates angiotensin II‐induced hypertension and endothelial dysfunction by inhibiting HDAC6‐mediated cystathionine γ‐lyase degradation |
title_fullStr | Honokiol ameliorates angiotensin II‐induced hypertension and endothelial dysfunction by inhibiting HDAC6‐mediated cystathionine γ‐lyase degradation |
title_full_unstemmed | Honokiol ameliorates angiotensin II‐induced hypertension and endothelial dysfunction by inhibiting HDAC6‐mediated cystathionine γ‐lyase degradation |
title_short | Honokiol ameliorates angiotensin II‐induced hypertension and endothelial dysfunction by inhibiting HDAC6‐mediated cystathionine γ‐lyase degradation |
title_sort | honokiol ameliorates angiotensin ii‐induced hypertension and endothelial dysfunction by inhibiting hdac6‐mediated cystathionine γ‐lyase degradation |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521302/ https://www.ncbi.nlm.nih.gov/pubmed/32755037 http://dx.doi.org/10.1111/jcmm.15686 |
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