Abstract:
:Although the depletion of reduced glutathione (GSH) has been observed in a variety of apoptotic systems, little is known about the mechanism of GSH depletion. In this study we used polarized MDCK cells to study the GSH flux during ricin-induced apoptosis. Here we report that the specific accumulation of GSH occurred in the basolateral medium during ricin treatment with similar kinetics to in apoptotic changes such as an increase in caspase-3 like activity and DNA fragmentation, while there was no significant increase in the GSH level in apical medium. These results suggest that GSH efflux occurred through a GSH-specific channel or transporter located in the basolateral membrane domain of polarized MDCK cells undergoing apoptosis. Treatment with other protein toxins such as modeccin, Pseudomonas toxin, and diphtheria toxin, which can induce apoptotic cell death, also resulted in selective GSH efflux from the basolateral side. Thus, GSH efflux through a specific transporter may be a common step of apoptosis induced by these toxins, while these toxins have different intoxication mechanisms leading to protein synthesis inhibition. Pretreatment of cells with Z-Asp-CH(2)-DCB, a caspase family inhibitor, inhibited ricin-induced basolateral GSH efflux as well as DNA fragmentation, suggesting that the activation of caspases, i.e. those that are inhibited by Z-Asp-CH(2)-DCB, is implicated in the opening of the GSH transporter.
journal_name
J Biochemjournal_title
Journal of biochemistryauthors
Oda T,Sadakata N,Komatsu N,Muramatsu Tdoi
10.1093/oxfordjournals.jbchem.a022508keywords:
subject
Has Abstractpub_date
1999-10-01 00:00:00pages
715-21issue
4eissn
0021-924Xissn
1756-2651journal_volume
126pub_type
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journal_title:Journal of biochemistry
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journal_title:Journal of biochemistry
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pub_type: 杂志文章
doi:10.1093/oxfordjournals.jbchem.a132805
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journal_title:Journal of biochemistry
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journal_title:Journal of biochemistry
pub_type: 杂志文章
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journal_title:Journal of biochemistry
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更新日期:2004-01-01 00:00:00