Proteomics

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Profiling of Methylglyoxal Blood Metabolism and Advanced Glycation End-Product Proteome using a Chemical Probe


ABSTRACT: Methylglyoxal (MG) is a toxic byproduct of the glycolytic pathway and is quantitatively the most important precursor to advanced glycation end-products (AGEs). Insight into which proteins and in particular their individual modification sites are central to understand the involvement of MG and AGE in diabetes and aging related diseases. Here, we present a method to simultaneously monitor protein AGE formation in biological samples by employing an alkyne-labeled methylglyoxal probe. We apply the method to blood and plasma to demonstrate the impact of blood cell glyoxalase activity on plasma protein AGE formation. We move on to isolate proteins modified by the MG probe and accordingly can present the first general inventory of more than 100 proteins and 300 binding sites of the methylglyoxal probe on plasma as well as erythrocytic proteins.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Erythrocyte, Blood Cell, Blood Plasma, Blood

SUBMITTER: Johan Palmfeldt  

LAB HEAD: Johan Palmfeldt

PROVIDER: PXD011314 | Pride | 2019-07-31

REPOSITORIES: Pride

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Profiling of Methylglyoxal Blood Metabolism and Advanced Glycation End-Product Proteome Using a Chemical Probe.

Sibbersen Christian C   Schou Oxvig Anne-Mette AM   Bisgaard Olesen Sarah S   Nielsen Camilla Bak CB   Galligan James J JJ   Jørgensen Karl Anker KA   Palmfeldt Johan J   Johannsen Mogens M  

ACS chemical biology 20181203 12


Methylglyoxal (MG) is quantitatively the most important precursor to advanced glycation end-products (AGEs), and evidence is accumulating that it is also a causally linked to diabetes and aging related diseases. Living systems primarily reside on the glyoxalase system to detoxify MG into benign d-lactate. The flux to either glycation or detoxification, accordingly, is a key parameter for how well a system handles the ubiquitous glyoxal burden. Furthermore, insight into proteins and in particular  ...[more]

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