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- Publisher Website: 10.1038/nchembio.1657
- Scopus: eid_2-s2.0-84924923805
- PMID: 25383758
- WOS: WOS:000346448600007
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Article: Terazosin activates Pgk1 and Hsp90 to promote stress resistance
Title | Terazosin activates Pgk1 and Hsp90 to promote stress resistance |
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Authors | |
Issue Date | 2015 |
Publisher | Nature 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? |
Abstract | Drugs 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 Identifier | http://hdl.handle.net/10722/221113 |
ISSN | 2023 Impact Factor: 12.9 2023 SCImago Journal Rankings: 5.558 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Chen, X | - |
dc.contributor.author | Zhao, C | - |
dc.contributor.author | Li, XL | - |
dc.contributor.author | Wang, T | - |
dc.contributor.author | Li, Y | - |
dc.contributor.author | Cao, C | - |
dc.contributor.author | Ding, Y | - |
dc.contributor.author | Dong, M | - |
dc.contributor.author | Finci, L | - |
dc.contributor.author | Wang, J | - |
dc.contributor.author | Li, X | - |
dc.contributor.author | Liu, L | - |
dc.date.accessioned | 2015-10-27T07:57:36Z | - |
dc.date.available | 2015-10-27T07:57:36Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Nature Chemical Biology, 2015, v. 11 n. 1, p. 19-25 | - |
dc.identifier.issn | 1552-4450 | - |
dc.identifier.uri | http://hdl.handle.net/10722/221113 | - |
dc.description.abstract | Drugs 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.language | eng | - |
dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/naturechemicalbiology | - |
dc.relation.ispartof | Nature Chemical Biology | - |
dc.title | Terazosin activates Pgk1 and Hsp90 to promote stress resistance | - |
dc.type | Article | - |
dc.identifier.email | Li, X: xiaoyuli@hku.hk | - |
dc.identifier.authority | Li, X=rp02080 | - |
dc.identifier.doi | 10.1038/nchembio.1657 | - |
dc.identifier.pmid | 25383758 | - |
dc.identifier.pmcid | PMC4412158 | - |
dc.identifier.scopus | eid_2-s2.0-84924923805 | - |
dc.identifier.hkuros | 274762 | - |
dc.identifier.volume | 11 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 19 | - |
dc.identifier.epage | 25 | - |
dc.identifier.isi | WOS:000346448600007 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 1552-4450 | - |