Human UDP-galactose 4′-epimerase (GALE) is required for cell-surface glycome structure and function

Broussard, Alex; Florwick, Alyssa; Desbiens, Chelsea; Nischan, Nicole; Robertson, Corrina; Guan, Ziqiang; Kohler, Jennifer J.; Wells, Lance; Boyce, Michael

doi:10.1016/s0021-9258(17)49882-6

Cited by 22 publications

(13 citation statements)

References 90 publications

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“…Direct nuclear modulation of gene transcription by HEXA is unlikely due to its lysosomal localization. Rather, the enzymatic activity of HEXA towards GM2 gangliosides leads to the cleavage of an N‐Acetyl‐beta‐D‐galactosamine (GalNAc), 60 which is converted to UDP‐GalNAc by galactose‐1‐phosphate uridylyltransferase, and further to UDP‐N‐acetylglucosamine (UDP‐GlcNAc) by UDP‐galactose‐4‐epimerase, 61 thus increasing the capacity for protein O‐GlcNAcylation, which is an important posttranslational modification that regulates the activity of hundreds of protein substrates involved in transcription, epigenetic modification and cell signalling dynamics 62 . Apob and Mttp expression are regulated by carbohydrate responsive‐element binding protein (ChREBP) 63 and the forkhead transcription factor FoxO1, 64 and these transcription factors are regulated through O‐GlcNAcylation 65,66 .…”

Section: Discussionmentioning

confidence: 99%

Hexosaminidase A (HEXA) regulates hepatic sphingolipid and lipoprotein metabolism in mice

et al. 2021

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Hexosaminidase A (HexA), a heterodimer consisting of HEXA and HEXB, converts the ganglioside sphingolipid GM2 to GM3 by removing a terminal N-acetyl-dgalactosamine. HexA enzyme deficiency in humans leads to GM2 accumulation in cells, particularly in neurons, and is associated with neurodegeneration. While HexA and sphingolipid metabolism have been extensively investigated in the context of neuronal lipid metabolism, little is known about the metabolic impact of HexA and ganglioside degradation in other tissues. Here, we focussed on the role of HexA in the liver, which is a major regulator of systemic lipid metabolism. We find that hepatic Hexa expression is induced by lipid availability and increased in the presence of hepatic steatosis, which is associated with increased hepatic GM3 content. To assess the impact of HEXA on hepatic lipid metabolism, we used an adeno-associated virus to overexpress HEXA in the livers of high-fat diet fed mice. HEXA overexpression was associated with increased hepatic GM3 content and increased expression of enzymes involved in the degradation of glycated sphingolipids, ultimately driving sphingomyelin accumulation in the liver. In addition, HEXA overexpression led to substantial proteome remodeling in cell surface lipid rafts, which was associated with increased VLDL processing and secretion, hypertriglyceridemia and ectopic lipid accumulation in peripheral tissues. This study established an important role of HEXA in modulating hepatic sphingolipid and lipoprotein metabolism.

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Section: Discussionmentioning

confidence: 99%

Hexosaminidase A (HEXA) regulates hepatic sphingolipid and lipoprotein metabolism in mice

et al. 2021

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“…A total of 99 active peptides with molecular weight between 500-1000 Da were detected in the broth of No.3, including 52 from Pichia and 49 from bi dobaterium shown in Supplementary Table . The 10 important peptides with the relative abundance over than 1% were shown in Table 4. For example, UDP-glucose 4-epimerase could induce the conformational change of gale, activate the reduction of NAD + , produce NADH and promote cell productivity (Broussard A et al, 2020). α-Larabinofuranosidase is the main glycosidase (a lignocellulose-degrading enzyme) that causes the degradation of arabinose residues in cell wall polysaccharides, which can improve the e ciency of fermenting sugars in plant biomass (Poria V et al, 2020).…”

Section: Proteomics Analysismentioning

confidence: 99%

Sequentially fermentation of traditional Chinese medicine by Pichia kudriavzevii and bifidobacteria for Skin Care Function

Pan

Yinglong

Zhang

et al. 2022

Preprint

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In order to explore the feasibility on Skin Care Function of fermentative traditional Chinese medicine, Pichia kudriavzevii strains isolated from Strong-flavor baijiu grains were used to ferment food homologous traditional Chinese medicine with the assistance of bifidobacterial. In the present study, we analyzed 16 Pichia kudriavzevii strains and 13 kinds of Chinese herbal medicines. Firstly, 9 Chinese herbal medicines were selected according the growth of bifidobacteria in the broth of 13 Chinese herbal medicines; then 9 Pichia kudriavzevii strains that could promote the growth of bifidobacteria were screened by the method of sequential fermentation in the 9 Chinese herbal medicines; after that, 9 Pichia kudriavzevii strains and bifidobacteria sequentially fermented the broth composed of the above 9 kinds of traditional Chinese medicine according to different formulas, and the moisture residual rate, hydroxyl radical scavenging rate and tyrosinase inhibition rate of the broth were detected to evaluate its skin care function. Better skin care function was found in the sequentially fermented broth of No.3 composed of Rhodiola, Raspberry, Bletilla striata, Atractylodes by YB07 and bifidobacterial, which displayed the moisture residual rate of 6.36%, the hydroxyl radical scavenging rate of 83.95% and the tyrosinase inhibition rate of 60.3%. Proteomic analysis by LC-MS showed this broth contained 99 active peptides (＜1000 Da) in skin lotion. 24h skin patch and 30-day skin safety test preliminarily revealed the safety of the fermentation broth as skin care products. This study provides a new perspective of food homologous traditional Chinese medicine for skin care products.

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“…Notably, a CS side chain of serum bikunin, CS-PG, from a patient with mutation in SLC35A3 was shorter than that from a control subject (Haouari et al, 2020). Because CS did not contain the GlcNAc residue, the finding indicates several possibilities that SLC35A3 transports UDP-GalNAc in addition to UDP-GlcNAc, and that UDP-GlcNAc-4 -epimerase/UDP-Gal-4 -epimerase encoded by GALE is located in the Golgi apparatus in addition to cytosol (Thoden et al, 2001;Broussard et al, 2020;Fushinobu, 2021).…”

Section: Arthrogryposis Intellectual Disability and Seizures Caused By Mutations In Slc35a3mentioning

confidence: 99%

Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis

Mizumoto

Yamada

2021

Front. Genet.

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Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, and heparan sulfate are covalently attached to specific core proteins to form proteoglycans, which are distributed at the cell surface as well as in the extracellular matrix. Proteoglycans and GAGs have been demonstrated to exhibit a variety of physiological functions such as construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, cytokines, and growth factors. Not only connective tissue disorders including skeletal dysplasia, chondrodysplasia, multiple exostoses, and Ehlers-Danlos syndrome, but also heart and kidney defects, immune deficiencies, and neurological abnormalities have been shown to be caused by defects in GAGs as well as core proteins of proteoglycans. These findings indicate that GAGs and proteoglycans are essential for human development in major organs. The glycobiological aspects of congenital disorders caused by defects in GAG-biosynthetic enzymes including specific glysocyltransferases, epimerases, and sulfotransferases, in addition to core proteins of proteoglycans will be comprehensively discussed based on the literature to date.

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Human UDP-galactose 4′-epimerase (GALE) is required for cell-surface glycome structure and function

Cited by 22 publications

References 90 publications

Hexosaminidase A (HEXA) regulates hepatic sphingolipid and lipoprotein metabolism in mice

Hexosaminidase A (HEXA) regulates hepatic sphingolipid and lipoprotein metabolism in mice

Sequentially fermentation of traditional Chinese medicine by Pichia kudriavzevii and bifidobacteria for Skin Care Function

Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis

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