Deleterious effects of reactive aldehydes and glycated proteins on macrophage proteasomal function: Possible links between diabetes and atherosclerosis

Fatemeh Moheimani, Philip E. Morgan, David M. van Reyk, Michael J. Davies

    Research output: Contribution to journalArticle

    28 Citations (Scopus)

    Abstract

    People with diabetes experience chronic hyperglycemia and are at a high risk of developing atherosclerosis and microvascular disease. Reactions of glucose, or aldehydes derived from glucose (e.g. methylglyoxal, glyoxal, or glycolaldehyde), with proteins result in glycation that ultimately yield advanced glycation end products (AGE). AGE are present at elevated levels in plasma and atherosclerotic lesions from people with diabetes, and previous in vitro studies have postulated that the presence of these materials is deleterious to cell function. This accumulation of AGE and glycated proteins within cells may arise from either increased formation and/or ineffective removal by cellular proteolytic systems, such as the proteasomes, the major multi-enzyme complex that removes proteins within cells. In this study it is shown that whilst high glucose concentrations fail to modify proteasome enzyme activities in J774A.1 macrophage-like cell extracts, reactive aldehydes enhanced proteasomal enzyme activities. In contrast BSA, pre-treated with high glucose for 8. weeks, inhibited both the chymotrypsin-like and caspase-like activities. BSA glycated using methylglyoxal or glycolaldehyde, also inhibited proteasomal activity though to differing extents. This suppression of proteasome activity by glycated proteins may result in further intracellular accumulation of glycated proteins with subsequent deleterious effects on cellular function.

    Original languageEnglish
    Pages (from-to)561-571
    Number of pages11
    JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
    Volume1802
    Issue number6
    DOIs
    Publication statusPublished - 1 Jun 2010

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