Enhanced activation of NAD(P)H:quinone oxidoreductase 1 attenuates spontaneous hypertension by improvement of endothelial nitric oxide synthase coupling via tumor suppressor kinase liver kinase B1/adenosine 5 '-monophosphate-activated protein kinase-mediated guanosine 5 '-triphosphate cyclohydrolase 1 preservation
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Yong-Hoon | - |
dc.contributor.author | Hwang, Jung Hwan | - |
dc.contributor.author | Kim, Kyung-Shim | - |
dc.contributor.author | Noh, Jung-Ran | - |
dc.contributor.author | Gang, Gil-Tae | - |
dc.contributor.author | Oh, Won Keun | - |
dc.contributor.author | Jeong, Kyeong-Hoon | - |
dc.contributor.author | Kwak, Tae Hwan | - |
dc.contributor.author | Choi, Hueng-Sik | - |
dc.contributor.author | Lee, In-Kyu | - |
dc.contributor.author | Lee, Chul-Ho | - |
dc.date.available | 2020-02-28T18:42:00Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2014-02 | - |
dc.identifier.issn | 0263-6352 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12855 | - |
dc.description.abstract | Aims:Guanosine 5-triphosphate cyclohydrolase-1 (GTPCH-1) is a rate-limiting enzyme in de-novo synthesis of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase (eNOS) coupling. Adenosine 5-monophosphate-activated protein kinase (AMPK) is crucial for GTPCH-1 preservation, and tumor suppressor kinase liver kinase B1 (LKB1), an upstream kinase of AMPK, is activated by NAD(+)-dependent class III histone deacetylase sirtuin 1 (SIRT1)-mediated deacetylation. -Lapachone has been shown to increase cellular NAD(+)/NADH ratio via NAD(P)H:quinone oxidoreductase 1 (NQO1) activation. In this study, we have evaluated whether -lapachone-induced NQO1 activation modulates blood pressure (BP) through preservation of GTPCH-1 in a hypertensive animal model.Methods and results:Spontaneously hypertensive rats (SHRs), primary aortic endothelial cells, and endothelial cell line were used to investigate the hypotensive effect of -lapachone and its action mechanism. -Lapachone treatment dramatically lowered BP and vascular tension in SHRs and induced eNOS activation in endothelial cells. Consistent with these effects, -lapachone treatment also elevated levels of both aortic cGMP and plasma nitric oxide in SHRs. Meanwhile, -lapachone-treated SHRs showed significantly increased levels of aortic NAD(+), LKB1 deacetylation, and AMPK Thr(172) phosphorylation followed by increased GTPCH-1 and tetrahydrobiopterin/dihydrobiopterin ratio. In-vitro study revealed that AMPK inhibition by overexpression of dominant-negative AMPK nearly abolished GTPCH-1 protein conservation. Enhanced LKB1 deacetylation and AMPK activation were also elicited by -lapachone in endothelial cells. However, inhibition of LKB1 deacetylation by blocking of NQO1 or SIRT1 blunted AMPK activation by -lapachone.Conclusion:This is the first study demonstrating that eNOS coupling can be regulated by NQO1 activation via LKB1/AMPK/GTPCH-1 modulation, which is possibly correlated with relieving hypertension. These findings provide strong evidence to suggest that NQO1 might be a new therapeutic target for hypertension. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | - |
dc.relation.isPartOf | JOURNAL OF HYPERTENSION | - |
dc.subject | HIGH BLOOD-PRESSURE | - |
dc.subject | CALORIE RESTRICTION | - |
dc.subject | SKELETAL-MUSCLE | - |
dc.subject | COMBINATION THERAPY | - |
dc.subject | SIGNALING PATHWAYS | - |
dc.subject | SIRT1 ACTIVITY | - |
dc.subject | EXERCISE | - |
dc.subject | TETRAHYDROBIOPTERIN | - |
dc.subject | CELLS | - |
dc.subject | AMPK | - |
dc.title | Enhanced activation of NAD(P)H:quinone oxidoreductase 1 attenuates spontaneous hypertension by improvement of endothelial nitric oxide synthase coupling via tumor suppressor kinase liver kinase B1/adenosine 5 '-monophosphate-activated protein kinase-mediated guanosine 5 '-triphosphate cyclohydrolase 1 preservation | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000330876000016 | - |
dc.identifier.doi | 10.1097/HJH.0000000000000018 | - |
dc.identifier.bibliographicCitation | JOURNAL OF HYPERTENSION, v.32, no.2, pp.306 - 317 | - |
dc.identifier.scopusid | 2-s2.0-84892985432 | - |
dc.citation.endPage | 317 | - |
dc.citation.startPage | 306 | - |
dc.citation.title | JOURNAL OF HYPERTENSION | - |
dc.citation.volume | 32 | - |
dc.citation.number | 2 | - |
dc.contributor.affiliatedAuthor | Jeong, Kyeong-Hoon | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | endothelial nitric oxide synthase | - |
dc.subject.keywordAuthor | guanosine 5 &apos | - |
dc.subject.keywordAuthor | -triphosphate cyclohydrolase-1 | - |
dc.subject.keywordAuthor | hypertension | - |
dc.subject.keywordAuthor | NAD(P)H:quinone oxidoreductase 1 | - |
dc.subject.keywordAuthor | tumor suppressor kinase liver kinase B1/adenosine 5 &apos | - |
dc.subject.keywordAuthor | -monophosphate-activated protein kinase | - |
dc.subject.keywordPlus | HIGH BLOOD-PRESSURE | - |
dc.subject.keywordPlus | CALORIE RESTRICTION | - |
dc.subject.keywordPlus | SKELETAL-MUSCLE | - |
dc.subject.keywordPlus | COMBINATION THERAPY | - |
dc.subject.keywordPlus | SIGNALING PATHWAYS | - |
dc.subject.keywordPlus | SIRT1 ACTIVITY | - |
dc.subject.keywordPlus | EXERCISE | - |
dc.subject.keywordPlus | TETRAHYDROBIOPTERIN | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | AMPK | - |
dc.relation.journalResearchArea | Cardiovascular System & Cardiology | - |
dc.relation.journalWebOfScienceCategory | Peripheral Vascular Disease | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea(13120)031-750-5114
COPYRIGHT 2020 Gachon University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.