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Article: Terazosin activates Pgk1 and Hsp90 to promote stress resistance

TitleTerazosin activates Pgk1 and Hsp90 to promote stress resistance
Authors
Issue Date2015
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturechemicalbiology
Citation
Nature Chemical Biology, 2015, v. 11 n. 1, p. 19-25 How to Cite?
AbstractDrugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We discovered that terazosin (TZ), a widely marketed α 1-adrenergic receptor antagonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we discovered that TZ binds a new target, phosphoglycerate kinase 1 (Pgk1), and activates its enzymatic activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multistress resistance. Our studies demonstrate that TZ has a new protein target, Pgk1, and reveal its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatments for diseases including stroke and sepsis. © 2015 Nature America, Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/221113
ISSN
2015 Impact Factor: 12.709
2015 SCImago Journal Rankings: 8.200
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, X-
dc.contributor.authorZhao, C-
dc.contributor.authorLi, XL-
dc.contributor.authorWang, T-
dc.contributor.authorLi, Y-
dc.contributor.authorCao, C-
dc.contributor.authorDing, Y-
dc.contributor.authorDong, M-
dc.contributor.authorFinci, L-
dc.contributor.authorWang, J-
dc.contributor.authorLi, X-
dc.contributor.authorLiu, L-
dc.date.accessioned2015-10-27T07:57:36Z-
dc.date.available2015-10-27T07:57:36Z-
dc.date.issued2015-
dc.identifier.citationNature Chemical Biology, 2015, v. 11 n. 1, p. 19-25-
dc.identifier.issn1552-4450-
dc.identifier.urihttp://hdl.handle.net/10722/221113-
dc.description.abstractDrugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We discovered that terazosin (TZ), a widely marketed α 1-adrenergic receptor antagonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we discovered that TZ binds a new target, phosphoglycerate kinase 1 (Pgk1), and activates its enzymatic activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multistress resistance. Our studies demonstrate that TZ has a new protein target, Pgk1, and reveal its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatments for diseases including stroke and sepsis. © 2015 Nature America, Inc. All rights reserved.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/naturechemicalbiology-
dc.relation.ispartofNature Chemical Biology-
dc.titleTerazosin activates Pgk1 and Hsp90 to promote stress resistance-
dc.typeArticle-
dc.identifier.emailLi, X: xiaoyuli@hku.hk-
dc.identifier.authorityLi, X=rp02080-
dc.identifier.doi10.1038/nchembio.1657-
dc.identifier.pmid25383758-
dc.identifier.scopuseid_2-s2.0-84924923805-
dc.identifier.volume11-
dc.identifier.issue1-
dc.identifier.spage19-
dc.identifier.epage25-
dc.identifier.isiWOS:000346448600007-
dc.publisher.placeUnited Kingdom-

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