| Autor: |
West JD; Biochemistry & Molecular Biology Program, Departments of Biology and Chemistry, The College of Wooster, Wooster, Ohio 44691, USA. jwest@wooster.edu, Stamm CE, Brown HA, Justice SL, Morano KA |
| Jazyk: |
angličtina |
| Zdroj: |
Chemical research in toxicology [Chem Res Toxicol] 2011 Sep 19; Vol. 24 (9), pp. 1457-9. Date of Electronic Publication: 2011 Aug 08. |
| DOI: |
10.1021/tx200302w |
| Abstrakt: |
Previously, we determined that diethyl acetylenedicarboxylate (DAD), a protein cross-linker, was significantly more toxic than analogous monofunctional electrophiles. We hypothesized that other protein cross-linkers enhance toxicity similarly. In agreement with this hypothesis, the bifunctional electrophile divinyl sulfone (DVSF) was 6-fold more toxic than ethyl vinyl sulfone (EVSF) in colorectal carcinoma cells and greater than 10-fold more toxic in Saccharomyces cerevisiae. DVSF and DAD caused oligomerization of yeast thioredoxin 2 (Trx2p) in vitro and promoted Trx2p cross-linking to other proteins in yeast at cytotoxic doses. Our results suggest that protein cross-linking is considerably more detrimental to cellular homeostasis than simple alkylation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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