Advanced Glycation End Products/Peptides: An in Vivo Investigation

Abstract

Advanced glycation end products/peptides (AGE/peptides) originate by in vivo enzymatic digestion of nonenzymatically glycated proteins, which are produced by reaction of glucose with primary amino groups present in the protein chain following the Maillard pattern. AGE/peptides are highly reactive species and can interact with tissue and circulating proteins, leading to tissue modification and impaired protein functionality. Serum levels of AGE/peptides are reported to be particularly high in diabetes (in terms of higher production) or in end-stage renal disease (in terms of accumulation). For these reasons, their structural identification is of high interest, giving information on their relationship with the pathological state and allowing the design of possible therapeutic interventions. We report here some preliminary results obtained by liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS) and matrix-assisted laser desorption ionization MS (MALDI-MS) investigations carried out on the low-molecular-weight serum peptide fraction from 10 healthy subjects, 10 patients with poorly controlled diabetes, and 10 patients with end-stage nephropathy.

The Glycocalyx Protects Erythrocyte-Bound Tissue-Type Plasminogen Activator from Enzymatic Inhibition

“…6A, inset). These data corroborate findings that tPA inhibition via nonenzymatic glycosylation/glycation requires a relatively prolonged (i.e., hours) exposure (Lapolla et al, 2005).…”

“…Interactions between RBC/tPA and the glycocalyx may jpet.aspetjournals.org mask the lysine residues in tPA molecules that are vulnerable to Maillard product formation and glycation (Lapolla et al, 2005).…”

Characterization of glycation adducts on human serum albumin by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

“…Further rearrangement and cleavage of this fructosamine can lead to other modifications, known as advanced glycation end products (AGEs). Figure 1 provides a summary of such products, as identified in previous work with HSA and other glycated proteins [6,[9][10][11][12][13][14][15][16][17][18][19][20].…”

“…Determining the locations and types of modifications that occur on glycated HSA would help give a better understanding of these effects. This study examined such modifications by using in vitro glycated HSA, which has proposed to be a good model for glycated HSA in serum and plasma [18,19]. The extent to which HSA can be glycated in vitro can range from minimal levels (<10 mol modification sites per mol protein) to high levels (30-40 mol modification sites per mol protein) [9,10], with previous studies indicating that minimally glycated HSA is the better model for individuals with well-controlled diabetics [11,17].…”

Methylglyoxal Activates Nociceptors through Transient Receptor Potential Channel A1 (TRPA1)

“…The exaggerated glycolytic metabolism resulting from hyperglycemia is known to activate and sensitize primary nociceptive neurons (7)(8)(9). Painful neuropathy also occurs in patients suffering from chronic renal failure that also involves elevated plasma levels of MG (6,10). In this pathological condition, "carbonyl stress" such as by MG has been considered to be responsible for many concomitant complications (11).…”