Abstract:
:Advanced glycation endproduct (AGE) formation is an important mechanism for protein deterioration during diabetic complications and ageing. The effects on AGE formation following dihydroxyacetone (DHA) stress were studied in two model organisms, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Total protein AGEs, detected using an anti-N(epsilon)-carboxyalkyllysine-specific monoclonal antibody, displayed a strong correlation to DHA-induced yeast cell mortality in the wild-type and hypersensitive as well as resistant mutant strains. During DHA-induced cell death we also detected AGEs as the formation of acidic protein modifications by 2-D PAGE. Furthermore, we confirmed AGE targets immunologically on 2-D gel-separated protein extracted from DHA-treated cells. AGE modification of several metabolic enzymes (Eno2p, Adh1p, Met6 and Pgk1p) and actin (Act1p) displayed a strong correlation to DHA-induced cell death. DHA was toxic to C. elegans even at low concentration and also in this organism AGE formation accompanied death. We propose the use of DHA as a model AGE-generating substance for its apparent lack of a clear oxidative stress connection, and yeast and worm as model organisms to identify genetic determinants of protein AGE formation.
journal_name
Proteomicsjournal_title
Proteomicsauthors
Molin M,Pilon M,Blomberg Adoi
10.1002/pmic.200700165subject
Has Abstractpub_date
2007-10-01 00:00:00pages
3764-74issue
20eissn
1615-9853issn
1615-9861journal_volume
7pub_type
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