Glycoconjugate journal
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Glycoconjugate journal · Aug 2016
ReviewImplication of advanced glycation end products (Ages) and their receptor (Rage) on myocardial contractile and mitochondrial functions.
Advanced glycation end products (AGEs) play an important role for the development and/or progression of cardiovascular diseases, mainly through induction of oxidative stress and inflammation. AGEs are a heterogeneous group of molecules formed by non-enzymatic reaction of reducing sugars with amino acids of proteins, lipids and nucleic acids. AGEs are mainly formed endogenously, while recent studies suggest that diet constitutes an important exogenous source of AGEs. ⋯ AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes up regulation of the transcription factor nuclear factor-κB and its target genes. of the RAGE engagement stimulates oxidative stress, evokes inflammatory and fibrotic reactions, which all contribute to the development and progression of devastating cardiovascular disorders. This review discusses potential targets of glycation in cardiac cells, and underlying mechanisms that lead to heart failure with special interest on AGE-induced mitochondrial dysfunction in the myocardium.
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Glycoconjugate journal · Aug 2016
DNA-aptamers raised against AGEs as a blocker of various aging-related disorders.
A non-enzymatic reaction between sugars or aldehydes and the amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules, which could impair their structural integrity and function. This process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions, such as rearrangements and dehydration to become irreversibly crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). ⋯ Furthermore, diet has been recently recognized as a major environmental source of AGEs that could also elicit pro-inflammatory reactions, thereby being involved in organ damage in vivo. Therefore, inhibition of AGE formation and/or blockade of the interaction of AGEs with RAGE may be a novel therapeutic target for aging-related disorders. This article discusses a potential utility of DNA-aptamers raised against AGEs for preventing aging and/or diabetes-associated organ damage, especially focusing on diabetic microvascular complications, vascular remodeling, metabolic derangements, and melanoma growth and expansion in animal models.