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Literature summary for 2.8.2.8 extracted from

  • Chen, H.; Ambadapadi, S.; Wakefield, D.; Bartee, M.; Yaron, J.R.; Zhang, L.; Archer-Hartmann, S.A.; Azadi, P.; Burgin, M.; Borges, C.; Zheng, D.; Ergle, K.; Muppala, V.; Morshed, S.; Rand, K.; Clapp, W.; Proudfoot, A.; Lucas, A.
    Selective deletion of heparan sulfotransferase enzyme, Ndst1, in donor endothelial and myeloid precursor cells significantly decreases acute allograft rejection (2018), Sci. Rep., 8, 13433 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
additional information construction of conditional deficiency of the glycocalyx-modifying enzyme N-deacetylase-N-sulfotransferase-1 (Ndst1f/f TekCre+) which reduces aortic allograft inflammation. Conditional donor allograft Ndst1 deficiency (Ndst1-/-, C57Bl/6 background) is compared to systemic treatment with M-T7, a broad-spectrum chemokine glycosaminoglycan (GAG) inhibitor. Early rejection is significantly reduced in Ndst1-/- kidneys engrafted into wild-type BALB/c mice (Ndst1+/+) and comparable to M-T7 treatment in C57Bl/6 allografts. M-T7 is a 37 kDa Myxomavirus-derived secreted glycoprotein that possesses both broad spectrum, species-independent, C, CC and CXC chemokine inhibitory activity and a rabbit species-specific interferon gamma (IFNgamma) inhibitory activity. M-T7 activity is blunted in Ndst1-deficient mouse donor aortic transplants, a model for chronic TAV and vascular injury, but not in CC chemokine receptor deficient aortic allograft transplants, supporting M-T7 interference with chemokine-GAG interactions. M-T7 loses activity in Ndst1-/- allografts, while M-T7 point mutants with modified GAG chemokine binding display a range of anti-rejection activity. CD3+ T cells, HS and CXC chemokine staining, gene expression in NFkappaB and JAK/STAT pathways, and HS and CS disaccharide content are significantly altered with reduced rejection Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
extracellular
-
Mus musculus
-
-
glycocalyx
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Mus musculus 30112
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine Mus musculus
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adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine Mus musculus C57BL/6
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adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus Q3UHN9
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-
Mus musculus C57BL/6 Q3UHN9
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-

Source Tissue

Source Tissue Comment Organism Textmining
aorta
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Mus musculus
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endothelial cell
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Mus musculus
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myeloid progenitor cell
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Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
-
Mus musculus adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
-
Mus musculus C57BL/6 adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine
-
?

Synonyms

Synonyms Comment Organism
glycocalyx-modifying enzyme
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Mus musculus
N-deacetylase-N-sulfotransferase-1
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Mus musculus
Ndst1
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Mus musculus

General Information

General Information Comment Organism
malfunction selective deletion of heparan sulfotransferase enzyme, Ndst1, in donor endothelial and myeloid precursor cells significantly decreases acute allograft rejection, overview. Ndst1 deficiency in donor renal allografts significantly reduces histopathological markers for early renal allograft rejection. M-T7 (Myxomavirus-derived secreted glycoprotein that possesses a broad spectrum, species-independent, C, CC and CXC chemokine inhibitory activity) treatment significantly reduces histopathological markers for renal allograft rejection. M-T7 and M-T7 point mutant treatment have variable efficacy in WT and Ndst1-/- allografts. Reduced HS and chemokine immunoreactivity is associated with reduced rejection Mus musculus
physiological function N-deacetylase-N-sulfotransferase-1 (Ndst1) acts as a central modifying enzyme in heparan sulfate (HS), catalyzing sulfate conjugation to carbohydrates. Modification of HS and chemokine interactions in whole-organ renal allografts, overview Mus musculus