Abstract：
:The antiinflammatory drug ebselen (2-phenyl-1,2-benzisoselenazo-3(2H)-one) is known to bind covalently to thiols to form seleno disulfides that, directly or indirectly, are responsible for its pharmacological effects. Due to its reactive thiol group and high plasma concentration, albumin is a preferred target of ebselen, which it binds covalently. Ebselen should not, then, be available for intracellular actions at other target proteins. We have addressed this question, and show by difference spectroscopy that the interaction of ebselen with albumin occurs stoichiometrically under ring opening, but is readily reversible in the presence of glutathione. With intact human polymorphonuclear leukocytes (PMN), a similar stoichiometric reaction with distinct spectral features was observed with ebselen that was completely abolished by pretreatment of PMN with N-ethylmaleimide, but not by selective depletion of cellular glutathione. Human platelets, again, exhibited different spectral changes upon addition of ebselen. In agreement with results reported in the literature, we show that 14C-ebselen is in dynamic equilibrium with all accessible thiol groups and, hence, despite mostly being bound covalently to albumin, it will exchange rapidly with other target proteins in PMN or platelets.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Ullrich V,Weber P,Meisch F,von Appen Fdoi
10.1016/0006-2952(96)00109-8subject
Has Abstractpub_date
1996-07-12 00:00:00pages
15-9issue
1eissn
0006-2952issn
1873-2968pii
0006295296001098journal_volume
52pub_type
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更新日期：2006-11-15 00:00:00
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pub_type： 杂志文章
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更新日期：1989-04-15 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2000-10-15 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：1996-04-12 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.12.012
更新日期：2008-04-01 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：1992-11-03 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：2012-07-01 00:00:00
