Show simple item record

AuthorRabbani, Naila
AuthorXue, Mingzhan
AuthorThornalley, Paul J.
Available date2023-03-27T08:37:04Z
Publication Date2021-06-01
Publication NameGlycoconjugate Journal
Identifierhttp://dx.doi.org/10.1007/s10719-021-09980-0
CitationRabbani, N., Xue, M. & Thornalley, P.J. Dicarbonyl stress, protein glycation and the unfolded protein response. Glycoconj J 38, 331–340 (2021). https://doi.org/10.1007/s10719-021-09980-0
ISSN02820080
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85101838039&origin=inward
URIhttp://hdl.handle.net/10576/41347
AbstractThe reactive dicarbonyl metabolite, methylglyoxal (MG), is increased in obesity and diabetes and is implicated in the development of insulin resistance, type 2 diabetes mellitus and vascular complications of diabetes. Dicarbonyl stress is the metabolic state of abnormal high MG concentration. MG is an arginine-directed glycating agent and precursor of the major advanced glycation endproduct, arginine-derived hydroimidazolone MG-H1. MG-H1 is often formed on protein surfaces and an uncharged hydrophobic residue, inducing protein structural distortion and misfolding. Recent studies indicate that dicarbonyl stress in human endothelial cells and fibroblasts in vitro induced a proteomic response consistent with activation of the unfolded protein response (UPR). The response included: increased abundance of heat shock proteins and ubiquitin ligases catalysing the removal of proteins with unshielded surface hydrophobic patches and formation of polyubiquitinated chains to encapsulate misfolded proteins; and increased low grade inflammation. Activation of the UPR is implicated in insulin resistance. An effective strategy to counter increased MG is inducing increased expression of glyoxalase-1 (Glo1). An optimized inducer of Glo1 expression, trans-resveratrol and hesperetin combination, normalized increased MG concentration, corrected insulin resistance and decreased low grade inflammation in overweight and obese subjects. We propose that dicarbonyl stress, through increased formation of MG-glycated proteins, may be an important physiological stimulus of the UPR and Glo1 inducers may provide a route to effective suppression and therapy. With further investigation and validation, this may provide key new insight into physiological activators of the UPR and association with dicarbonyl stress.
SponsorOpen access funding provided by the Qatar National Library.
Languageen
PublisherSpringer
SubjectGlycation
Glyoxalase
Heat shock response
Insulin resistance
Low grade inflammation
Methylglyoxal
Ubiquitin ligase
Unfolded protein response
TitleDicarbonyl stress, protein glycation and the unfolded protein response
TypeArticle Review
Pagination331-340
Issue Number3
Volume Number38
ESSN1573-4986
dc.accessType Open Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record