Cargando…

Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension

Numerous studies have indicated that a high salt diet inhibits brain Na(+)/K(+)-ATPase (NKA) activity, and affects oxidative stress and inflammation in the paraventricular nucleus (PVN). Furthermore, Na(+)/K(+)-ATPase alpha 2-isoform (NKA α2) may be a target in the brain, taking part in the developm...

Descripción completa

Detalles Bibliográficos
Autores principales: Su, Qing, Yu, Xiao-Jing, Wang, Xiao-Min, Peng, Bo, Bai, Juan, Li, Hong-Bao, Li, Ying, Xia, Wen-Jie, Fu, Li-Yan, Liu, Kai-Li, Liu, Jin-Jun, Kang, Yu-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868219/
https://www.ncbi.nlm.nih.gov/pubmed/35204171
http://dx.doi.org/10.3390/antiox11020288
_version_ 1784656214179708928
author Su, Qing
Yu, Xiao-Jing
Wang, Xiao-Min
Peng, Bo
Bai, Juan
Li, Hong-Bao
Li, Ying
Xia, Wen-Jie
Fu, Li-Yan
Liu, Kai-Li
Liu, Jin-Jun
Kang, Yu-Ming
author_facet Su, Qing
Yu, Xiao-Jing
Wang, Xiao-Min
Peng, Bo
Bai, Juan
Li, Hong-Bao
Li, Ying
Xia, Wen-Jie
Fu, Li-Yan
Liu, Kai-Li
Liu, Jin-Jun
Kang, Yu-Ming
author_sort Su, Qing
collection PubMed
description Numerous studies have indicated that a high salt diet inhibits brain Na(+)/K(+)-ATPase (NKA) activity, and affects oxidative stress and inflammation in the paraventricular nucleus (PVN). Furthermore, Na(+)/K(+)-ATPase alpha 2-isoform (NKA α2) may be a target in the brain, taking part in the development of salt-dependent hypertension. Therefore, we hypothesized that NKA α2 regulates oxidative stress and inflammation in the PVN in the context of salt-induced hypertension. Part I: We assessed NKA subunits (NKA α1, NKA α2, and NKA α3), Na(+)/K(+)-ATPase activity, oxidative stress, and inflammation in a high salt group (8% NaCl) and normal salt group (0.3% NaCl). Part II: NKA α2 short hairpin RNA (shRNA) was bilaterally microinjected into the PVN of salt-induced hypertensive rats to knockdown NKA α2, and we explored whether NKA α2 regulates downstream signaling pathways related to protein kinase C γ (PKC γ)-dependent oxidative stress and toll-like receptor 4 (TLR4)-induced inflammation in the PVN to promote the development of hypertension. High salt diet increased NKA α1 and NKA α2 protein expression in the PVN but had no effect on NKA α3 compared to the normal salt diet. Na(+)/K(+)-ATPase activity and ADP/ATP ratio was lower, but NAD(P)H activity and NF-κB activity in the PVN were higher after a high salt diet. Bilateral PVN microinjection of NKA α2 shRNA not only improved Na(+)/K(+)-ATPase activity and ADP/ATP ratio but also suppressed PKC γ-dependent oxidative stress and TLR4-dependent inflammation in the PVN, thus decreasing sympathetic activity in rats with salt-induced hypertension. NKA α2 in the PVN elicits PKC γ/Rac1/NAD (P)H-dependent oxidative stress and TLR4/MyD88/NF-κB-induced inflammation in the PVN, thus increasing MAP and sympathetic activity during the development of salt-induced hypertension.
format Online
Article
Text
id pubmed-8868219
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88682192022-02-25 Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension Su, Qing Yu, Xiao-Jing Wang, Xiao-Min Peng, Bo Bai, Juan Li, Hong-Bao Li, Ying Xia, Wen-Jie Fu, Li-Yan Liu, Kai-Li Liu, Jin-Jun Kang, Yu-Ming Antioxidants (Basel) Article Numerous studies have indicated that a high salt diet inhibits brain Na(+)/K(+)-ATPase (NKA) activity, and affects oxidative stress and inflammation in the paraventricular nucleus (PVN). Furthermore, Na(+)/K(+)-ATPase alpha 2-isoform (NKA α2) may be a target in the brain, taking part in the development of salt-dependent hypertension. Therefore, we hypothesized that NKA α2 regulates oxidative stress and inflammation in the PVN in the context of salt-induced hypertension. Part I: We assessed NKA subunits (NKA α1, NKA α2, and NKA α3), Na(+)/K(+)-ATPase activity, oxidative stress, and inflammation in a high salt group (8% NaCl) and normal salt group (0.3% NaCl). Part II: NKA α2 short hairpin RNA (shRNA) was bilaterally microinjected into the PVN of salt-induced hypertensive rats to knockdown NKA α2, and we explored whether NKA α2 regulates downstream signaling pathways related to protein kinase C γ (PKC γ)-dependent oxidative stress and toll-like receptor 4 (TLR4)-induced inflammation in the PVN to promote the development of hypertension. High salt diet increased NKA α1 and NKA α2 protein expression in the PVN but had no effect on NKA α3 compared to the normal salt diet. Na(+)/K(+)-ATPase activity and ADP/ATP ratio was lower, but NAD(P)H activity and NF-κB activity in the PVN were higher after a high salt diet. Bilateral PVN microinjection of NKA α2 shRNA not only improved Na(+)/K(+)-ATPase activity and ADP/ATP ratio but also suppressed PKC γ-dependent oxidative stress and TLR4-dependent inflammation in the PVN, thus decreasing sympathetic activity in rats with salt-induced hypertension. NKA α2 in the PVN elicits PKC γ/Rac1/NAD (P)H-dependent oxidative stress and TLR4/MyD88/NF-κB-induced inflammation in the PVN, thus increasing MAP and sympathetic activity during the development of salt-induced hypertension. MDPI 2022-01-31 /pmc/articles/PMC8868219/ /pubmed/35204171 http://dx.doi.org/10.3390/antiox11020288 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Su, Qing
Yu, Xiao-Jing
Wang, Xiao-Min
Peng, Bo
Bai, Juan
Li, Hong-Bao
Li, Ying
Xia, Wen-Jie
Fu, Li-Yan
Liu, Kai-Li
Liu, Jin-Jun
Kang, Yu-Ming
Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension
title Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension
title_full Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension
title_fullStr Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension
title_full_unstemmed Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension
title_short Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension
title_sort na(+)/k(+)-atpase alpha 2 isoform elicits rac1-dependent oxidative stress and tlr4-induced inflammation in the hypothalamic paraventricular nucleus in high salt-induced hypertension
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868219/
https://www.ncbi.nlm.nih.gov/pubmed/35204171
http://dx.doi.org/10.3390/antiox11020288
work_keys_str_mv AT suqing nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT yuxiaojing nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT wangxiaomin nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT pengbo nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT baijuan nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT lihongbao nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT liying nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT xiawenjie nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT fuliyan nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT liukaili nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT liujinjun nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension
AT kangyuming nakatpasealpha2isoformelicitsrac1dependentoxidativestressandtlr4inducedinflammationinthehypothalamicparaventricularnucleusinhighsaltinducedhypertension