Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gene knock-out of C-type lectin receptors expressed in dendritic cells induced significant alteration of serum N-glycans compared with that of gender-matched controls. Glycotyping analysis suggested that putative-core fucosylation is strongly influenced by differences in the dominant mechanisms after carbohydrate recognition by pattern-recognition receptors, endocytosis of ligands, or induction of cytokines/chemokines. However, the loss of galectin-9, a ligand for T-helper type 1-specific cell-surface molecule, did not affect most N-glycan profiles. Interestingly, lack of the Chst3 gene (chondroitin 6-sulfotransferase) appeared to influence markedly the expression of most N-glycans, especially highly modified glycoforms bearing multiple Neu5Gc, Fuc, and LacNAc units. In contrast, genetic mutations in B4galnt1 and B4galnt2 (GalNAc transferase, responsible for the synthesis of many gangliosides) induced no discernable alteration. These results indicate that the biosynthesis of N-glycans of serum glycoproteins can be affected not only by direct genetic mutations in the glycosyltransferases but also by changes in metabolite availability in sugar nucleotide synthesis and Golgi N-glycosylation pathways caused concertedly in whole cells, tissues, and organs by milder deficiencies in immune cell-surface lectins. Many common chronic conditions, such as autoimmunity, metabolic syndrome, and aging/dementia result.
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PMID:Effects of single genetic damage in carbohydrate-recognizing proteins in mouse serum N-glycan profile revealed by simple glycotyping analysis. 2227 23

Glycan biosynthesis relies on nucleotide sugars (NSs), abundant metabolites that serve as monosaccharide donors for glycosyltransferases. In vivo, signal-dependent fluctuations in NS levels are required to maintain normal cell physiology and are dysregulated in disease. However, how mammalian cells regulate NS levels and pathway flux remains largely uncharacterized. To address this knowledge gap, here we examined UDP-galactose 4'-epimerase (GALE), which interconverts two pairs of essential NSs. Using immunoblotting, flow cytometry, and LC-MS-based glycolipid and glycan profiling, we found that CRISPR/Cas9-mediated GALE deletion in human cells triggers major imbalances in NSs and dramatic changes in glycolipids and glycoproteins, including a subset of integrins and the cell-surface death receptor FS-7-associated surface antigen. In particular, we observed substantial decreases in total sialic acid, galactose, and GalNAc levels in glycans. These changes also directly impacted cell signaling, as GALE -/- cells exhibited FS-7-associated surface antigen ligand-induced apoptosis. Our results reveal a role of GALE-mediated NS regulation in death receptor signaling and may have implications for the molecular etiology of illnesses characterized by NS imbalances, including galactosemia and metabolic syndrome.
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PMID:Human UDP-galactose 4'-epimerase (GALE) is required for cell-surface glycome structure and function. 3181 7

Probiotics are widely used for treatment of various human diseases, and their spectrum is not limited by intestinal diseases only. That is why there is a growing interest in the development of new probiotics that can modify intestinal microbiome in accordance with the needs for treatment. In 2004, Akkermansia muciniphila was discovered, and later it was shown to prevent the development of metabolic syndrome and diabetes mellitus in mice. Nevertheless, before using it for treatment, conditions necessary for its growth need to be identified. In particular, certain carbohydrates, including amino sugars, such as N-acetylglucosamine and N-acetylgalactosamine, were discovered to be necessary for successful cultivation of A. muciniphila in vitro. This is not surprising, since the natural habitat of A. muciniphila is intestinal mucin, which contains different amino sugars. Besides, ways of A. muciniphila protection from harmful factors on the way to the intestine have been developed. In addition, prebiotics such as oligosaccharides, polyphenols, as well as metformin used for diabetes mellitus treatment can promote its growth in the intestine. Finally, there is the first evidence of A. muciniphila administration to humans, which confirms the safety of its use and describes positive metabolic effects. Overall, these data suggest the possibility of an early introduction of this next-generation probiotic into clinical practice.
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PMID:Cultivation of the Next-Generation Probiotic Akkermansia muciniphila, Methods of Its Safe Delivery to the Intestine, and Factors Contributing to Its Growth In Vivo. 3231 63