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β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension

Oxidative stress in the rostral ventrolateral medulla (RVLM), a key region for blood pressure (BP) regulation, has been demonstrated to be responsible for the overactivity of the sympathetic nervous system in hypertension and heart failure. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is a key...

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Autores principales: Tan, Xing, Jiao, Pei-Lei, Sun, Jia-Cen, Wang, Wen, Ye, Peng, Wang, Yang-Kai, Leng, Yue-Qi, Wang, Wei-Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059792/
https://www.ncbi.nlm.nih.gov/pubmed/33897365
http://dx.doi.org/10.3389/fnins.2021.657825
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author Tan, Xing
Jiao, Pei-Lei
Sun, Jia-Cen
Wang, Wen
Ye, Peng
Wang, Yang-Kai
Leng, Yue-Qi
Wang, Wei-Zhong
author_facet Tan, Xing
Jiao, Pei-Lei
Sun, Jia-Cen
Wang, Wen
Ye, Peng
Wang, Yang-Kai
Leng, Yue-Qi
Wang, Wei-Zhong
author_sort Tan, Xing
collection PubMed
description Oxidative stress in the rostral ventrolateral medulla (RVLM), a key region for blood pressure (BP) regulation, has been demonstrated to be responsible for the overactivity of the sympathetic nervous system in hypertension and heart failure. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is a key transcription factor that maintains redox homeostasis by governing a broad array of antioxidant genes in response to oxidative stress. β-Arrestin1 is a multifunctional scaffold protein with the ability to interact with diverse signaling molecules independent of G protein-coupled receptors (GPCRs), and its overexpression in the RVLM could reduce BP and renal sympathetic nerve activity (RSNA) in spontaneously hypertensive rats (SHR). The goal of this study was to investigate whether Nrf2-mediated antioxidative stress is involved in the antihypertensive effect of β-arrestin1 in the RVLM. It was found that the activation level of Nrf2 in the RVLM of SHR was significantly reduced, compared with normotensive Wistar-Kyoko (WKY) rats. Overexpression of β-arrestin1 in the RVLM significantly decreased ROS production and facilitated the Nrf2 activation in the RVLM of SHR, accompanied by upregulating the expression of HO-1 and NQO-1. However, Nrf2 knockdown attenuated the antioxidant effect of β-arrestin1 overexpression in the RVLM by downregulating HO-1 and NQO-1 expression levels. In conclusion, the current results suggested that the antihypertensive effect of β-arrestin1 overexpression in the RVLM is mediated by decreased ROS production, which is associated with Nrf2 activation.
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spelling pubmed-80597922021-04-22 β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension Tan, Xing Jiao, Pei-Lei Sun, Jia-Cen Wang, Wen Ye, Peng Wang, Yang-Kai Leng, Yue-Qi Wang, Wei-Zhong Front Neurosci Neuroscience Oxidative stress in the rostral ventrolateral medulla (RVLM), a key region for blood pressure (BP) regulation, has been demonstrated to be responsible for the overactivity of the sympathetic nervous system in hypertension and heart failure. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is a key transcription factor that maintains redox homeostasis by governing a broad array of antioxidant genes in response to oxidative stress. β-Arrestin1 is a multifunctional scaffold protein with the ability to interact with diverse signaling molecules independent of G protein-coupled receptors (GPCRs), and its overexpression in the RVLM could reduce BP and renal sympathetic nerve activity (RSNA) in spontaneously hypertensive rats (SHR). The goal of this study was to investigate whether Nrf2-mediated antioxidative stress is involved in the antihypertensive effect of β-arrestin1 in the RVLM. It was found that the activation level of Nrf2 in the RVLM of SHR was significantly reduced, compared with normotensive Wistar-Kyoko (WKY) rats. Overexpression of β-arrestin1 in the RVLM significantly decreased ROS production and facilitated the Nrf2 activation in the RVLM of SHR, accompanied by upregulating the expression of HO-1 and NQO-1. However, Nrf2 knockdown attenuated the antioxidant effect of β-arrestin1 overexpression in the RVLM by downregulating HO-1 and NQO-1 expression levels. In conclusion, the current results suggested that the antihypertensive effect of β-arrestin1 overexpression in the RVLM is mediated by decreased ROS production, which is associated with Nrf2 activation. Frontiers Media S.A. 2021-04-07 /pmc/articles/PMC8059792/ /pubmed/33897365 http://dx.doi.org/10.3389/fnins.2021.657825 Text en Copyright © 2021 Tan, Jiao, Sun, Wang, Ye, Wang, Leng and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Tan, Xing
Jiao, Pei-Lei
Sun, Jia-Cen
Wang, Wen
Ye, Peng
Wang, Yang-Kai
Leng, Yue-Qi
Wang, Wei-Zhong
β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension
title β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension
title_full β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension
title_fullStr β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension
title_full_unstemmed β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension
title_short β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension
title_sort β-arrestin1 reduces oxidative stress via nrf2 activation in the rostral ventrolateral medulla in hypertension
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059792/
https://www.ncbi.nlm.nih.gov/pubmed/33897365
http://dx.doi.org/10.3389/fnins.2021.657825
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