Synthesis of an Alkynyl Methylglyoxal Probe to Investigate Nonenzymatic Histone Glycation.
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ABSTRACT:
SUBMITTER: Zheng Q
PROVIDER: S-EPMC8018604 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
2019-07-31 | PXD011314 | Pride
Project description:The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I.Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-I(N)), lipid-free apoA-I nonenzymatically glycated by incubation with methylglyoxal (apoA-I(Glyc in vitro)), nonenzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I(Glyc in vivo)), discoidal reconstituted high-density lipoproteins (rHDL) containing phosphatidylcholine and apoA-I(N), (A-I(N))rHDL, or apoA-I(Glyc in vitro), (A-I(Glyc in vitro))rHDL. At 24 hours postinfusion, acute vascular inflammation was induced by inserting a nonocclusive, periarterial carotid collar. The animals were euthanized 24 hours after the insertion of the collar. The collars caused intima/media neutrophil infiltration and increased endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). ApoA-I(N) infusion decreased neutrophil infiltration and VCAM-1 and ICAM-1 expression by 89%, 90%, and 66%, respectively. The apoA-I(Glyc in vitro) infusion decreased neutrophil infiltration by 53% but did not reduce VCAM-1 or ICAM-1 expression. ApoA-I(Glyc in vivo) did not inhibit neutrophil infiltration or adhesion molecule expression. (A-I(Glyc in vitro))rHDL also inhibited vascular inflammation less effectively than (A-I(N))rHDL. The reduced antiinflammatory properties of nonenzymatically glycated apoA-I were attributed to a reduced ability to inhibit nuclear factor-kappaB activation and reactive oxygen species formation.Nonenzymatic glycation impairs the antiinflammatory properties of apoA-I.
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