Maillard reaction in food allergy: Pros and cons Gupta, Rinkesh Kumar; Gupta, Kriti; Sharma, Akanksha ...
Critical reviews in food science and nutrition,
01/2018, Volume:
58, Issue:
2
Journal Article
Peer reviewed
Food allergens have a notable potential to induce various health concerns in susceptible individuals. The majority of allergenic foods are usually subjected to thermal processing prior to their ...consumption. However, during thermal processing and long storage of foods, Maillard reaction (MR) often takes place. The MR is a non-enzymatic glycation reaction between the carbonyl group of reducing sugars and compounds having free amino groups. MR may sometimes be beneficial by damaging epitope of allergens and reducing allergenic potential, while exacerbation in allergic reactions may also occur due to changes in the motifs of epitopes or neoallergen generation. Apart from these modulations, non-enzymatic glycation can also modify the food protein(s) with various type of advance glycation end products (AGEs) such as Nϵ-(carboxymethyl-)lysine (CML), pentosidine, pyrraline, and methylglyoxal-H1 derived from MR. These Maillard products may act as immunogen by inducing the activation and proliferation of various immune cells. Literature is available to understand pathogenesis of glycation in the context of various diseases but there is hardly any review that can provide a thorough insight on the impact of glycation in food allergy. Therefore, present review explores the pathogenesis with special reference to food allergy caused by non-enzymatic glycation as well as AGEs.
Advanced glycation end products (AGEs) are potentially harmful and heterogeneous molecules derived from nonenzymatic glycation. The pathological implications of AGEs are ascribed to their ability to ...promote oxidative stress, inflammation, and apoptosis. Recent studies in basic and translational research have revealed the contributing roles of AGEs in the development and progression of various aging-related pathological conditions, such as diabetes, cardiovascular complications, gut microbiome-associated illnesses, liver or neurodegenerative diseases, and cancer. Excessive chronic and/or acute binge consumption of alcohol (ethanol), a widely consumed addictive substance, is known to cause more than 200 diseases, including alcohol use disorder (addiction), alcoholic liver disease, and brain damage. However, despite the considerable amount of research in this area, the underlying molecular mechanisms by which alcohol abuse causes cellular toxicity and organ damage remain to be further characterized. In this review, we first briefly describe the properties of AGEs: their formation, accumulation, and receptor interactions. We then focus on the causative functions of AGEs that impact various aging-related diseases. We also highlight the biological connection of AGE-alcohol-adduct formations to alcohol-mediated tissue injury. Finally, we describe the potential translational research opportunities for treatment of various AGE- and/or alcohol-related adduct-associated disorders according to the mechanistic insights presented.
Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the adult population and is now a major cause of liver disease-related premature illness and deaths in the world. Treatment is largely ...based on lifestyle modification, which is difficult to achieve in most patients. Progression of simple fatty liver or steatosis to its severe form non-alcoholic steatohepatitis (NASH) and liver fibrosis has been explained by a 'two-hit hypothesis'. Whilst simple steatosis is considered the first hit, its transformation to NASH may be driven by a second hit. Of several factors that constitute the second hit, advanced glycation end products (AGEs), which are formed when reducing-sugars react with proteins or lipids, have been implicated as major candidates that drive steatosis to NASH via the receptor for AGEs (RAGE). Both endogenous and processed food-derived (exogenous) AGEs can activate RAGE, mainly present on Kupffer cells and hepatic stellate cells, thus propagating NAFLD progression. This review focuses on the pathophysiology of NAFLD with special emphasis on the role of food-derived AGEs in NAFLD progression to NASH and liver fibrosis. Moreover, the effect of dietary manipulation to reduce AGE content in food or the therapies targeting AGE/RAGE pathway on disease progression is also discussed.
Purpose
The severity of untreated or refractory diabetes mellitus has been functionally linked to elevated concentrations of free plasma glucose, clinically defined as hyperglycemia. Operationally, ...the pathophysiological presentations of prolonged hyperglycemia may be categorized within insulin-dependent and insulin-independent, type 1 and type 2 diabetic phenotypes, respectively. Accordingly, major areas of empirical biomedical research have focused on the elucidation of underlying mechanisms driving key cellular signaling systems that are significantly altered in patients presenting with diabetes-associated chronic hyperglycemia.
Methods
Presently, we provide a translationally oriented review of key studies evaluating the aberrant effects of hyperglycemia on two major signaling pathways linked to debilitating cellular and systemic effects via targeted disruption of mitochondrial bioenergetics: (1) advanced glycation end-products (AGEs)/and their cognate receptor for advanced glycation end-products (RAGEs), and (2) the hexosamine biosynthetic pathway (HBP).
Results
In preclinical models, cultured vascular endothelial cells exposed to hyperglycemic glucose concentrations were observed to produce enhanced levels of reactive oxygen species (ROS) functionally linked to increased formation of AGEs and expression of their cognate RAGEs. Importantly, inhibitors of AGEs formation, mitochondrial complex II, or un-couplers of oxidative phosphorylation, were observed to significantly reduce the effects of hyperglycemia on ROS production and cellular damage, thereby establishing a critical linkage to multiple levels of mitochondrial functioning. Hyperglycemia-mediated enhancement of mitochondrial ROS/superoxide production in vascular endothelial cells has been functionally linked to the shunting of glucose into the HBP with resultant long-term activation of pro-inflammatory signaling processes. Additionally, exposure of cultured cells to hyperglycemic conditions resulted in enhanced HBP-mediated inhibition of protein subunits of mitochondrial respiratory complexes I, III, and IV, intimately associated with normative cellular bioenergetics and ATP production.
Conclusions
Convergent lines of evidence link chronic hyperglycemic conditions to aberrant expression of AGEs/RAGEs and HBP signaling pathways in relation to the pathophysiological formation of ROS and pro-inflammatory processes on the functional dysregulation of mitochondrial bioenergetics.
Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, ...excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.
Traditionally the scene of some of London’s poorest, most crime-ridden neighborhoods, the East End of London has long been misunderstood as abject and deviant. As a landing place for migrants and ...newcomers, however, it has also been memorably and colorfully represented in the literature of Victorian authors such as Charles Dickens and Oscar Wilde. In Strangers in the Archive, Heidi Kaufman applies the resources of archives both material and digital to move beyond icon and stereotype to reveal a deeper understanding of East End literature and culture in the Victorian age.
Kaufman uncovers this engaging new perspective on the East End through Maria Polack’s Fiction without Romance (1830), the first novel to be published by an English Jew, and through records of Polack’s vibrant community. Although scholars of nineteenth-century London and readers of East End fictions persist in privileging sensational narratives of Jack the Ripper and the infamous Fagin the Jew as signs of universal depravity among East End minority ethnic and racial groups, Strangers in the Archive considers how archival materials are uniquely capable of redressing cultural silences and marginalized perspectives as well as reshaping conceptions of the global significance of literary and print culture in nineteenth-century London.
Many of this book’s subjects—including digital editions of rare books and manuscript diaries, multimedia maps, and other related East End print records—can be viewed online at the Lyon Archive and the Polack Archive.
We addressed the involvement of the receptor for advanced glycation end products (RAGE) in the impairment of the cellular cholesterol efflux elicited by glycated albumin. Albumin was isolated from ...type 1 (DM1) and type 2 (DM2) diabetes mellitus (HbA1c > 9%) and non-DM subjects (C). Moreover, albumin was glycated in vitro (AGE-albumin). Macrophages from
null and wild-type (WT) mice, or THP-1 transfected with siRNA-
were treated with C, DM1, DM2, non-glycated or AGE-albumin. The cholesterol efflux was reduced in WT cells exposed to DM1 or DM2 albumin as compared to C, and the intracellular lipid content was increased. These events were not observed in
null cells, in which the cholesterol efflux and lipid staining were, respectively, higher and lower when compared to WT cells. In WT,
,
and
mRNA increased and
and
diminished after treatment with DM1 and DM2 albumin. In
null cells treated with DM-albumin,
,
and
were reduced and
and
increased. In
-silenced THP-1,
and
mRNA were reduced and
and
were increased even after treatment with AGE or DM-albumin. RAGE mediates the deleterious effects of AGE-albumin in macrophage cholesterol efflux.
Abstract
Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases ...including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions; (2) to elucidate the molecular basis of their biological effects; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation.
DNA double‐strand breaks are a threat to genome integrity and cell viability. The nucleolytic processing of broken DNA ends plays a central role in dictating the repair processes that will mend these ...lesions. Usually, DNA end resection promotes repair by homologous recombination, whereas minimally processed ends are repaired by non‐homologous end joining. Important in this process is the chromatin‐binding protein 53BP1, which inhibits DNA end resection. How 53BP1 shields DNA ends from nucleases has been an enduring mystery. The recent discovery of shieldin, a four‐subunit protein complex with single‐stranded DNA‐binding activity, illuminated a strong candidate for the ultimate effector of 53BP1‐dependent end protection. Shieldin consists of REV7, a known 53BP1‐pathway component, and three hitherto uncharacterized proteins: C20orf196 (SHLD1), FAM35A (SHLD2), and CTC‐534A2.2 (SHLD3). Shieldin promotes many 53BP1‐associated activities, such as the protection of DNA ends, non‐homologous end joining, and immunoglobulin class switching. This review summarizes the identification of shieldin and the various models of shieldin action and highlights some outstanding questions requiring answers to gain a full molecular understanding of shieldin function.
How 53BP1 shields DNA ends from resection has been a mystery. This review summarizes the recent discovery of the protein complex shieldin, and how it promotes 53BP1 activities, such as DNA end protection, NHEJ and Ig class switching.
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