Dihydroxyacetone-induced death is accompanied by advanced glycation endproduct formation in selected proteins of Saccharomyces cerevisiae and Caenorhabditis elegans.

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

Proteomics

journal_title

Proteomics

authors

Molin M,Pilon M,Blomberg A

doi

10.1002/pmic.200700165

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

3764-74

issue

20

eissn

1615-9853

issn

1615-9861

journal_volume

7

pub_type

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