Amides are novel protein modifications formed by physiological sugars

Glomb, Marcus A.; Pfahler, Christoph

doi:10.1016/s0531-5131(02)00905-6

Cited by 16 publications

(29 citation statements)

References 4 publications

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“…K2P, MOLD, glucosepane, etc.) can reach levels up to 7.5 nmol/mg of lens protein in cataractous lenses and 4.1 nmol/mg of lens protein in aged human lenses (ages 60 years old and older) [16][17][18][19][20][21][22][23][24][25][57][58][59][60][61][62][63][64][65][66]. It should be noted that most of these AGEs have been detected in WI lens proteins and may represent a contributory factor in lens protein unfolding and aggregation.…”

Section: Discussionmentioning

confidence: 99%

Glycation by ascorbic acid oxidation products leads to the aggregation of lens proteins

Linetsky

Shipova

Cheng

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Previous studies from this laboratory have shown that there are striking similarities between the yellow chromophores, fluorophores and modified amino acids released by proteolytic digestion from calf lens proteins ascorbylated in vitro and their counterparts isolated from aged and cataractous lens proteins. The studies reported in this communication were conducted to further investigate whether ascorbic acid-mediated modification of lens proteins could lead to the formation of lens protein aggregates capable of scattering visible light, similar to the high molecular aggregates found in aged human lenses. Ascorbic acid, but not glucose, fructose, ribose or erythrulose, caused the aggregation of calf lens proteins to proteins ranging from 2.2 x 10(6) up to 3.0 x 10(8 )Da. This compared to proteins ranging from 1.8 x 10(6) up to 3.6 x 10(8 )Da for the water-soluble (WS) proteins isolated from aged human lenses. This aggregation was likely due to the glycation of lens crystallins because [U-(14)C] ascorbate was incorporated into the aggregate fraction and because NaCNBH(3), which reduces the initial Schiff base, prevented any protein aggregation. Reactions of ascorbate with purified crystallin fractions showed little or no aggregation of alpha-crystallin, significant aggregation of beta(H)-crystallin, but rapid precipitation of purified beta(L)- and gamma-crystallin. The aggregation of lens proteins can be prevented by the binding of damaged crystallins to alpha-crystallin due to its chaperone activity. Depending upon the ratios between the components of the incubation mixtures, alpha-crystallin prevented the precipitation of the purified beta(L)- and gamma-crystallin fractions during ascorbylation. The addition of at least 20% of alpha-crystallin by weight into glycation mixtures with beta(L)-, or gamma-crystallins completely inhibited protein precipitation, and increased the amount of the high molecular weight aggregates in solution. Static and dynamic light scattering measurements of the supernatants from the ascorbic acid-modified mixtures of alpha- and beta(L)-, or gamma-crystallins showed similar molar masses (up to 10(8 )Da) and hydrodynamic diameter (up to 80( )nm). These data support the hypothesis, that if the lens reducing environment is compromised, the ascorbylation of lens crystallins can significantly change the short range interactions between different classes of crystallins leading to protein aggregation, light scattering and eventually to senile cataract formation.

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Section: Discussionmentioning

confidence: 99%

Glycation by ascorbic acid oxidation products leads to the aggregation of lens proteins

Linetsky

Shipova

Cheng

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Most of the linear or cross‐linked AGE derivatives reported in Figure were initially discovered by LC‐MS‐, GC‐MS‐, or LC‐ESI‐MS/MS‐based procedures, which were developed ad hoc and applied to the analysis of liquid foods, biological fluids (urine and plasma), or protein hydrolysates from solid (pharmaceutical, food, or tissue) samples previously subjected to acid or extensive enzymatic hydrolysis. Thus, different methods for partial and/or concomitant detection of these compounds were developed (Nakamura, Nakazawa, & Ienaga, ; Niwa et al, ; Odani et al, ; Glomb & Pfahler, ; Biemel et al, ; Glomb, Rosch, & Nagaraj, ; Odani et al, ; Biemel, Friedl, & Lederer, ; Tessier et al, ; Thornalley et al, ; Sell & Monnier, ; Teerlink et al, ; Sell et al, ; Dai et al, ; Schettgen et al, ; Assar et al, ; Delatour et al, ; Han et al, ; Henning et al, ; Nemet, Strauch, & Monnier, ; Sroga et al, ; Willett et al, ). Some AGEs, for example, dihydroxyimidazolines and hydroimidazolones, are not stable to extensive acid hydrolysis and were only detected under specific conditions.…”

Section: Mass Spectrometry Methods For Quantitative Evaluation Of Agementioning

confidence: 99%

Non‐enzymatic glycation and glycoxidation protein products in foods and diseases: An interconnected, complex scenario fully open to innovative proteomic studies

Arena

Salzano

Renzone

et al. 2013

Mass Spectrometry Reviews

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The Maillard reaction includes a complex network of processes affecting food and biopharmaceutical products; it also occurs in living organisms and has been strictly related to cell aging, to the pathogenesis of several (chronic) diseases, such as diabetes, uremia, cataract, liver cirrhosis and various neurodegenerative pathologies, as well as to peritoneal dialysis treatment. Dozens of compounds are involved in this process, among which a number of protein-adducted derivatives that have been simplistically defined as early, intermediate and advanced glycation end-products. In the last decade, various bottom-up proteomic approaches have been successfully used for the identification of glycation/glycoxidation protein targets as well as for the characterization of the corresponding adducts, including assignment of the modified amino acids. This article provides an updated overview of the mass spectrometry-based procedures developed to this purpose, emphasizing their partial limits with respect to current proteomic approaches for the analysis of other post-translational modifications. These limitations are mainly related to the concomitant sheer diversity, chemical complexity, and variable abundance of the various derivatives to be characterized. Some challenges to scientists are finally proposed for future proteomic investigations to solve main drawbacks in this research field.

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“…Previous work identified dysregulation of mitochondrial processes, increased inflammation, and the reduced degradation of proteins by the ubiquitin-proteasome system as results of glycation [10][11][12] . A special subtype are the amide AGEs, which are lysine acylation structures formed independently from enzymes by glycation 13 . Recently, reactive acyl-CoA species were identified as sources of non-enzymatic lysine acylation, while acylphosphates were hypothesized as a third pathway of non-enzymatic acylation 14 .…”

mentioning

confidence: 99%

Comprehensive analysis of posttranslational protein modifications in aging of subcellular compartments

Baldensperger

Eggen

Kappen

et al. 2020

Sci Rep

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Enzymatic and non-enzymatic posttranslational protein modifications by oxidation, glycation and acylation are key regulatory mechanisms in hallmarks of aging like inflammation, altered epigenetics and decline in proteostasis. In this study a mouse cohort was used to monitor changes of posttranslational modifications in the aging process. A protocol for the extraction of histones, cytosolic and mitochondrial proteins from mouse liver was developed and validated. In total, 6 lysine acylation structures, 7 advanced glycation endproducts, 6 oxidative stress markers, and citrullination were quantitated in proteins of subcellular compartments using HPLC-MS/MS. Methionine sulfoxide, acetylation, formylation, and citrullination were the most abundant modifications. Histone proteins were extraordinary high modified and non-enzymatic modifications accumulated in all subcellular compartments during the aging process. Compared to acetylation of histone proteins which gave between 350 and 305 µmol/mol leucine equivalents in young and old animals, modifications like acylation, glycation, and citrullination raised to 43%, 20%, and 18% of acetylation, respectively. On the other hand there was an age related increase of selected oxidative stress markers by up to 150%. The data and patterns measured in this study are mandatory for further studies and will strongly facilitate understanding of the molecular mechanisms in aging.

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Amides are novel protein modifications formed by physiological sugars

Cited by 16 publications

References 4 publications

Glycation by ascorbic acid oxidation products leads to the aggregation of lens proteins

Glycation by ascorbic acid oxidation products leads to the aggregation of lens proteins

Non‐enzymatic glycation and glycoxidation protein products in foods and diseases: An interconnected, complex scenario fully open to innovative proteomic studies

Comprehensive analysis of posttranslational protein modifications in aging of subcellular compartments

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