scholarly journals Glycation of Plant Proteins: Regulatory Roles and Interplay with Sugar Signalling?

2019 ◽  
Vol 20 (9) ◽  
pp. 2366 ◽  
Author(s):  
Julia Shumilina ◽  
Alena Kusnetsova ◽  
Alexander Tsarev ◽  
Henry C. Janse van Rensburg ◽  
Sergei Medvedev ◽  
...  
Keyword(s):  
Oxidative Degradation ◽  
Physiological Role ◽  
Protein Glycation ◽  
Plant Proteins ◽  
Post Translational Modifications ◽  
Sugar Signalling ◽  
Glycation End Products ◽  
Carbohydrate Contents ◽  
Carbonyl Products

Glycation can be defined as an array of non-enzymatic post-translational modifications of proteins formed by their interaction with reducing carbohydrates and carbonyl products of their degradation. Initial steps of this process rely on reducing sugars and result in the formation of early glycation products—Amadori and Heyns compounds via Schiff base intermediates, whereas their oxidative degradation or reactions of proteins with α-dicarbonyl compounds yield a heterogeneous group of advanced glycation end products (AGEs). These compounds accompany thermal processing of protein-containing foods and are known to impact on ageing, pathogenesis of diabetes mellitus and Alzheimer’s disease in mammals. Surprisingly, despite high tissue carbohydrate contents, glycation of plant proteins was addressed only recently and its physiological role in plants is still not understood. Therefore, here we summarize and critically discuss the first steps done in the field of plant protein glycation during the last decade. We consider the main features of plant glycated proteome and discuss them in the context of characteristic metabolic background. Further, we address the possible role of protein glycation in plants and consider its probable contribution to protein degradation, methylglyoxal and sugar signalling, as well as interplay with antioxidant defense.

scholarly journals RIPK1-Associated Inborn Errors of Innate Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahui Zhang ◽  
Taijie Jin ◽  
Ivona Aksentijevich ◽  
Qing Zhou
Keyword(s):  
Immune Deficiency ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Physiological Role ◽  
Model Organisms ◽  
Loss Of Function ◽  
Inborn Errors ◽  
Post Translational Modifications ◽  
Cell Death Signaling

RIPK1 (receptor-interacting serine/threonine-protein kinase 1) is a key molecule for mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors (DRs) and pattern recognition receptors (PRRs). RIPK1 functions are regulated by multiple post-translational modifications (PTMs), including ubiquitination, phosphorylation, and the caspase-8-mediated cleavage. Dysregulation of these modifications leads to an immune deficiency or a hyperinflammatory disease in humans. Over the last decades, numerous studies on the RIPK1 function in model organisms have provided insights into the molecular mechanisms of RIPK1 role in the maintenance of immune homeostasis. However, the physiological role of RIPK1 in the regulation of cell survival and cell death signaling in humans remained elusive. Recently, RIPK1 loss-of-function (LoF) mutations and cleavage-deficient mutations have been identified in humans. This review discusses the molecular pathogenesis of RIPK1-deficiency and cleavage-resistant RIPK1 induced autoinflammatory (CRIA) disorders and summarizes the clinical manifestations of respective diseases to help with the identification of new patients.

scholarly journals Drought-related Changes in the Metabolism and Nutritional Properties of Mature Pea (Pisum sativum L.) Seeds in the Context of Protein Glycation

2019 ◽  
Author(s):  
Tatiana Leonova ◽  
Veronika Popova ◽  
Alexander Tsarev ◽  
Christian Henning ◽  
Kristina Antonova ◽  
...  
Keyword(s):  
Seed Protein ◽  
Metabolic Diseases ◽  
Biological Activities ◽  
Neuroblastoma Cells ◽  
Protein Glycation ◽  
Short Term ◽  
Post Translational Modifications ◽  
Seed Filling ◽  
Glycation End Products ◽  
Covalent Adducts

Protein glycation is usually referred to as an array of non-enzymatic post-translational modifications, formed by reducing sugars and carbonyl products of their degradation. Resulting advanced glycation end products (AGEs) represent a heterogeneous group of covalent adducts, known for their pro-inflammatory effects in mammals, and impacting on pathogenesis of metabolic diseases and ageing. In plants, AGEs are the markers of tissue ageing and response to environmental stressors, the most prominent of which is drought. Although water deficit enhances protein glycation in leaves, its effect on seed glycation profiles is still unknown. Moreover, the effect of drought on biological activities of seed protein in mammalian systems is still unstudied in respect of glycation. Therefore, here we address the effects of a short-term drought on the patterns of seed protein-bound AGEs and accompanying alterations in pro-inflammatory properties of seed protein in the context of seed metabolome dynamics. A short-term drought, simulated as polyethylene glycol-induced osmotic stress and applied at the stage of seed filling, resulted in dramatic suppression of primary seed metabolism, although secondary metabolome was minimally affected. This was accompanied with significant suppression of NF-kB activation in human SH-SY5Y neuroblastoma cells after a treatment with protein hydrolyzates, isolated from the mature seeds of drought-treated plants. This effect could not be attributed to formation of known AGEs. Most likely, the prospective anti-inflammatory effect of short-term drought is related to antioxidant effect of unknown secondary metabolite protein adducts, or down-regulation of unknown plant-specific AGEs due to suppression of energy metabolism during seed filling.

Glycation in food and metabolic transit of dietary AGEs (advanced glycation end-products): studies on the urinary excretion of pyrraline

2003 ◽  
Vol 31 (6) ◽  
pp. 1383-1385 ◽  
Author(s):  
A. Foerster ◽  
T. Henle
Keyword(s):  
Urinary Excretion ◽  
Advanced Glycation End Products ◽  
Physiological Role ◽  
Dietary Control ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
First Time

Pyrraline [∊-(2´-formyl-5´-hydroxymethyl-pyrrolyl)-l-norleucin] belongs to the group of AGEs (advanced glycation end-products) formed in the final stage of the Maillard reaction in foods and in vivo. As it is generally accepted that AGEs are pathophysiologically relevant in aging and in diseases such as diabetes and uraemia, physiological consequences resulting from the ingestion of dietary AGEs are discussed, but balance studies for well defined AGEs are still lacking. The aim of our study was to investigate the influence of nutrition on the urinary excretion of pyrraline. After the first day without dietary restrictions, seven healthy volunteers were asked, starting on the morning of day 2, to ingest a diet virtually free of Maillard compounds (i.e. no cooked or roasted foods, no bakery products, no coffee, etc.). Dietary control was stopped on the morning of day 5. We collected 24 h urine samples for these 5 days, which were analysed for free pyrraline by reverse-phase HPLC with UV detection at 297 nm. We found that urinary excretion of free pyrraline was directly affected by the composition of the diet, decreasing from 4.8±1.1 mg/day on day 1 to levels of 1.6, 0.4 and 0.3 mg/day on days 2, 3 and 4 respectively, followed by a significant increase to 3.2±1.4 mg/day on the 5th day. The results of this work prove, for the first time, that urinary excretion of pyrraline is strongly dependent on its dietary intake. Thus the influence of nutrition should be taken into consideration in studies directed to the physiological role of glycation compounds.

scholarly journals Hydroxytyrosol Selectively Affects Non-Enzymatic Glycation in Human Insulin and Protects by AGEs Cytotoxicity

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1127
Author(s):  
Ivana Sirangelo ◽  
Margherita Borriello ◽  
Maria Liccardo ◽  
Marika Scafuro ◽  
Paola Russo ◽  
...  
Keyword(s):  
Human Insulin ◽  
Neurodegenerative Disorders ◽  
Cell Biology ◽  
Protein Glycation ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

Hydroxytyrosol (HT), the major phenolic compound in olive oil, is attracting increasing interest for its beneficial properties including a notable antioxidant and anti-inflammatory power. In this study, using a combination of biophysical and cell biology techniques, we have tested the role of HT in the formation of advanced glycation end-products (AGEs). AGEs have a key role in clinical sciences as they have been associated to diabetes, neurodegenerative and cardiovascular diseases. In addition, as the incidence of Alzheimer’s disease (AD) is strongly increased in diabetic patients, AGE formation is supposed to be involved in the development of the pathological hallmarks of AD. Our data show that HT selectively inhibits protein glycation reaction in human insulin, and it is able to counteract the AGE-induced cytotoxicity in human neurotypical cells by acting on SIRT1 level and oxidative stress, as well as on inflammatory response. This study identifies new beneficial properties for HT and suggests it might be a promising molecule in protecting against the AGE-induced toxicity, a key mechanism underlying the development and progression of neurodegenerative disorders.

Methylglyoxal, oxidative stress, and hypertension

2006 ◽  
Vol 84 (12) ◽  
pp. 1229-1238 ◽  
Author(s):  
Tuanjie Chang ◽  
Lingyun Wu
Keyword(s):  
Oxidative Stress ◽  
Protein Glycation ◽  
Ros Production ◽  
Oxygen Species ◽  
Advanced Glycation ◽  
Chain Reaction ◽  
Research Teams ◽  
Glycation End Products ◽  
End Products

Pathogenic mechanisms for essential hypertension are unclear despite striking efforts from numerous research teams over several decades. Increased production of reactive oxygen species (ROS) has been associated with the development of hypertension and the role of ROS in hypertension has been well documented in recent years. In this context, it is important to better understand pathways and triggering factors for increased ROS production in hypertension. This review draws a causative linkage between elevated methylglyoxal level, methylglyoxal-induced production of ROS, and advanced glycation end products in the development of hypertension. It is proposed that elevated methylglyoxal level and resulting protein glycation and ROS production may be the upstream links in the chain reaction leading to the development of hypertension.

scholarly journals Does Protein Glycation Impact on the Drought-Related Changes in Metabolism and Nutritional Properties of Mature Pea (Pisum sativum L.) Seeds?

2020 ◽  
Vol 21 (2) ◽  
pp. 567 ◽  
Author(s):  
Tatiana Leonova ◽  
Veronika Popova ◽  
Alexander Tsarev ◽  
Christian Henning ◽  
Kristina Antonova ◽  
...  
Keyword(s):  
Seed Protein ◽  
Metabolic Diseases ◽  
Biological Activities ◽  
Neuroblastoma Cells ◽  
Protein Glycation ◽  
Short Term ◽  
Post Translational Modifications ◽  
Seed Filling ◽  
Glycation End Products ◽  
Covalent Adducts

Protein glycation is usually referred to as an array of non-enzymatic post-translational modifications formed by reducing sugars and carbonyl products of their degradation. The resulting advanced glycation end products (AGEs) represent a heterogeneous group of covalent adducts, known for their pro-inflammatory effects in mammals, and impacting on pathogenesis of metabolic diseases and ageing. In plants, AGEs are the markers of tissue ageing and response to environmental stressors, the most prominent of which is drought. Although water deficit enhances protein glycation in leaves, its effect on seed glycation profiles is still unknown. Moreover, the effect of drought on biological activities of seed protein in mammalian systems is still unstudied with respect to glycation. Therefore, here we address the effects of a short-term drought on the patterns of seed protein-bound AGEs and accompanying alterations in pro-inflammatory properties of seed protein in the context of seed metabolome dynamics. A short-term drought, simulated as polyethylene glycol-induced osmotic stress and applied at the stage of seed filling, resulted in the dramatic suppression of primary seed metabolism, although the secondary metabolome was minimally affected. This was accompanied with significant suppression of NF-kB activation in human SH-SY5Y neuroblastoma cells after a treatment with protein hydrolyzates, isolated from the mature seeds of drought-treated plants. This effect could not be attributed to formation of known AGEs. Most likely, the prospective anti-inflammatory effect of short-term drought is related to antioxidant effect of unknown secondary metabolite protein adducts, or down-regulation of unknown plant-specific AGEs due to suppression of energy metabolism during seed filling.

scholarly journals Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer’s Disease

2021 ◽  
Vol 22 (17) ◽  
pp. 9461
Author(s):  
Jan Aaseth ◽  
Anatoly V. Skalny ◽  
Per M. Roos ◽  
Jan Alexander ◽  
Michael Aschner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Wide Spectrum ◽  
Protein Glycation ◽  
Special Focus ◽  
Fenton Chemistry ◽  
Glycation End Products ◽  
Aβ Generation ◽  
Rage Expression

The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer’s disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aβ generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroinflammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aβ cross-linking and up-regulation of RAGE expression. Moreover, Aβ glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenuate the intracellular toxicity of the deranged tau and Aβ, as well as inhibiting AGE accumulation and metal-induced neurotoxicity.

scholarly journals PTRF/Cavin-1 promotes efficient ribosomal RNA transcription in response to metabolic challenges

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Libin Liu ◽  
Paul F Pilch
Keyword(s):  
Cell Growth ◽  
Ribosomal Rna ◽  
Ribosome Biogenesis ◽  
Critical Role ◽  
Physiological Role ◽  
Rna Transcription ◽  
Post Translational Modifications ◽  
Acute Response ◽  
Polymerase I

Ribosomal RNA transcription mediated by RNA polymerase I represents the rate-limiting step in ribosome biogenesis. In eukaryotic cells, nutrients and growth factors regulate ribosomal RNA transcription through various key factors coupled to cell growth. We show here in mature adipocytes, ribosomal transcription can be acutely regulated in response to metabolic challenges. This acute response is mediated by PTRF (polymerase I transcription and release factor, also known as cavin-1), which has previously been shown to play a critical role in caveolae formation. The caveolae–independent rDNA transcriptional role of PTRF not only explains the lipodystrophy phenotype observed in PTRF deficient mice and humans, but also highlights its crucial physiological role in maintaining adipocyte allostasis. Multiple post-translational modifications of PTRF provide mechanistic bases for its regulation. The role of PTRF in ribosomal transcriptional efficiency is likely relevant to many additional physiological situations of cell growth and organismal metabolism.

scholarly journals Pigment-epithelium-derived factor (PEDF) occurs at a physiologically relevant concentration in human blood: purification and characterization

2003 ◽  
Vol 374 (1) ◽  
pp. 199-206 ◽  
Author(s):  
Steen V. PETERSEN ◽  
Zuzana VALNICKOVA ◽  
Jan J. ENGHILD
Keyword(s):  
Pigment Epithelium ◽  
Protein A ◽  
Physiological Role ◽  
The Body ◽  
Systemic Delivery ◽  
Blocking Group ◽  
Post Translational Modifications ◽  
Pigment Epithelium Derived Factor ◽  
Vessel Growth

Pigment epithelium-derived factor (PEDF) inhibits the formation of blood vessels in the eye by inducing apotosis in actively dividing endothelial cells. The activity of PEDF equals or supersedes that of other anti-angiogenic factors, including angiostatin, endostatin and thrombospondin-1. In addition, PEDF has the potential to promote the survival of neurons and affect their differentiation. Here we show that PEDF is present in plasma at a concentration of approx. 100 nM (5 μg/ml) or twice the level required to inhibit aberrant blood-vessel growth in the eye. Thus the systemic delivery of PEDF has the potential to affect angiogenesis or neurotrophic processes throughout the body, significantly expanding the putative physiological role of the protein. A complete map of all post-translational modifications revealed that authentic plasma PEDF carries an N-terminal pyroglutamate blocking group and an N-linked glycan at position Asn266. The pyroglutamate residue may regulate the activity of PEDF analogously to the manner in which it regulates thyrotropin-releasing hormone.

Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease

2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen
Keyword(s):  
Mass Spectrometry ◽  
Future Research ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Dicarbonyl Compounds ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Reactive Protein ◽  
Glycation End Products ◽  
Direct Mass Spectrometry

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.

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