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 · Jun 2016
ReviewA case for protein-level and site-level specificity in glycoproteomic studies of disease.
Abnormal glycosylation of proteins is known to be either resultant or causative of a variety of diseases. This makes glycoproteins appealing targets as potential biomarkers and focal points of molecular studies on the development and progression of human ailment. To date, a majority of efforts in disease glycoproteomics have tended to center on either determining the concentration of a given glycoprotein, or on profiling the total population of glycans released from a mixture of glycoproteins. ⋯ In this concise review, the rationale for glycoprotein and glycosylation site specificity is developed in the context of human disease glycoproteomics with an emphasis on N-glycosylation. Recent examples highlighting disease-related perturbations in glycosylation will be presented, including those involving alterations in the overall glycosylation of a specific protein, alterations in the occupancy of a given glycosylation site, and alterations in the compositional heterogeneity of glycans occurring at a given glycosylation site. Each will be discussed with particular emphasis on how protein-specific and site-specific approaches can contribute to improved discrimination between glycoproteomes and glycoproteins associated with healthy and unhealthy states.
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The majority of all proteins are glycosylated and glycans have numerous important structural, functional and regulatory roles in various physiological processes. While structure of the polypeptide part of a glycoprotein is defined by the sequence of nucleotides in the corresponding gene, structure of a glycan part results from dynamic interactions between hundreds of genes, their protein products and environmental factors. The composition of the glycome attached to an individual protein, or to a complex mixture of proteins, like human plasma, is stable within an individual, but very variable between individuals. ⋯ The epigenetic information (DNA methylation pattern and histone code) is especially vulnerable to environmental effects in the early intrauterine and neo-natal development and many common late-onset diseases take root already at that time. The evidences showing the link between epigenetics and glycosylation are accumulating. Recent progress in high-throughput glycomics, genomics and epigenomics enabled first epidemiological and genome-wide association studies of the glycome, which are presented in this mini-review.
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Glycoconjugate journal · Jan 2013
ReviewTherapies and therapeutic approaches in Congenital Disorders of Glycosylation.
Inborn errors in glycoconjugate biosynthesis termed 'Congenital Disorders of Glycosylation' (CDG) comprise a rapidly expanding group of metabolic diseases in man. Up till now more than 60 different inherited disorders in N- and O-glycosylation pathways have been identified. ⋯ Although improved biochemical and genetic investigations led to identification of a variety of new molecular defects in glycoconjugate biosynthesis, effective therapies for most types of the CDG are so far not available. Therefore, intensive investigations on treatment options for this group of diseases have been carried out in recent years.