Abstract：
:Inflammatory events are tightly associated with the death caused by Herpes simplex virus 1 (HSV-1) infection of the brain. Heat shock protein 90 (Hsp90) is a molecular chaperone that is stimulated in response to many stressful conditions (e.g., inflammation and hypoxia) and Hsp90 inhibitors are suggested to be potent inhibitors of the inflammatory response. The aim of this study was to investigate the effect of Hsp90 inhibitor AT-533 on HSV-1-induced inflammation. AT-533 at a non-antiviral concentration was found to show a prominent inhibitory effect on the production of cytokines induced by HSV-1 infection, such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and interleukin 1β (IL-1β). Mechanically, HSV-1 early infection induced inflammation through NF-κB signaling and NLRP3 inflammasome activation, as illustrated by the nuclear translocation of NF-κB and the enhanced cleavage of caspase-1. Besides, HSV-1 enhanced the interaction between NLRP3 and Hsp90. Moreover, AT-533 reduced the nuclear translocation of NF-κB and inflammasome activation via inhibiting the chaperone function of Hsp90. Furthermore, AT-533 inhibited the cleavage of pro-IL-1β to mature IL-1β in a NLRP3-independent manner. In summary, AT-533 may be a promising therapeutic strategy in HSV-1-infected inflammation management.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Li F,Song X,Su G,Wang Y,Wang Z,Qing S,Jia J,Wang Y,Huang L,Zheng K,Wang Ydoi
10.1016/j.bcp.2019.05.003subject
Has Abstractpub_date
2019-08-01 00:00:00pages
82-92eissn
0006-2952issn
1873-2968pii
S0006-2952(19)30167-4journal_volume
166pub_type
杂志文章abstract：:We investigated the interactions of 4'-(9-acridinylamino)methanesulfon-m-anisidide (mAMSA) with thiol-containing compounds and the potential binding of the thiolytic adducts to DNA. All thiols tested (glutathione, cysteine, coenzyme A, 2-mercaptoethanol and lactate dehydrogenase) formed adducts with mAMSA as evidenced...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90697-j
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90315-8
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.05.007
更新日期：2007-08-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00878-4
更新日期：2002-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.03.033
更新日期：2004-07-15 00:00:00
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pub_type： 杂志文章
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更新日期：1994-07-19 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.08.024
更新日期：2011-12-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2016-10-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90466-x
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1987-03-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2019-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2020-12-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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更新日期：2013-07-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90394-x
更新日期：1992-08-18 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90800-3
更新日期：1988-04-01 00:00:00
abstract：:Nitroimidazoles labeled with technetium-99m are being investigated as non-invasive markers of tumor hypoxia. They are bioreductive compounds that require enzymatic reduction for retention in hypoxic cells, but little is known about the cellular factors affecting their accumulation in hypoxic cells. If the absolute acc...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00373-7
更新日期：2000-09-01 00:00:00
abstract：:Previous reports have indicated that insulin administration triggers an early increase in plasma tryptophan (TRP) levels in fasted rats. Then, the present study was undertaken to investigate the putative role of liver tryptophan pyrrolase (TPO) in this short-term effect of insulin. In 24 hr fasted rats, doses of insul...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90312-9
更新日期：1990-08-15 00:00:00
