Altered glycosidase Activities at Physiological pH in the Pathogenesis of Sepsis

Aziz P, Haslund-Gourley B, Heithoff D, Westman J, Restagno D, Lewis B, Fried J, Ilse M-B, Lübke T, Marth J (2020)
In: FASEB JOURNAL., 34(S1). Hoboken: Wiley.

Kurzbeitrag Konferenz / Poster | Veröffentlicht | Englisch
 
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Autor*in
Aziz, Peter; Haslund-Gourley, Benjamin; Heithoff, Douglas; Westman, Julia; Restagno, Damien; Lewis, Benjamin; Fried, Jeffrey; Ilse, Mai-Britt; Lübke, TorbenUniBi; Marth, Jamey
Abstract / Bemerkung
Glycosidases are hydrolytic enzymes that are primarily studied in the context of intracellular catabolic pathways within the lysosome. Reductions in circulating glycosidase activities have been linked to lysosomal storage diseases and are typically detected in the blood acidified to mimic lysosomal pH. There are also instances of lysosomal storage diseases linked to increased glycosidase activities in blood circulation wherein the mannose‐6‐phosphate‐dependent trafficking is rendered dysfunctional. In addition, changes in circulating glycosidase activities have been associated with other syndromes including cancer, arthritis, alcohol abuse, sepsis, and colitis. We recently discovered that glycosidases present in multiple cell types and the sera and plasma are involved in the aging of secreted and cell surface glycoproteins. The exo‐glycosidase activities of endogenous circulating glycosidases generate the stepwise loss of glycan linkages over time as glycoproteins age in circulation, sequentially exposing underlying glycan linkages starting with the removal of the terminally‐positioned sialic acids. More is known of the neuraminidases in this first step and the role of asialoglycoprotein lectin receptors that can bind and endocytose the previously underlying and cryptic galactose ligands. We have optimized the detection of glycosidases involving those with galactosidase, glucosaminidase, mannosidase, and fucosidase activities using fluorimetric substrates in blood serum and plasma at physiological pH 7.4. We found all four glycosidase activities significantly above background in the blood and plasma at normal basal levels among healthy mouse and human species. We also identify the source of these glycosidases using glycosidase‐deficient mouse strains. We further present these measurements of normality and origin in comparison with measurements made during the onset and progression of sepsis caused by different pathogens in mice and humans. Our findings to be presented include the determinations of specific activities of glycosidases in response to experimental sepsis in the mouse caused by each of the five different clinically‐derived bacterial pathogens, and the discovery of a specific change in glycosidase activity statistically linked to a poor outcome (death) in human sepsis patients.
Erscheinungsjahr
2020
Titel des Konferenzbandes
FASEB JOURNAL
Band
34
Ausgabe
S1
Konferenz
Annual Meeting on Experimental Biology
Konferenzort
San Diego, CA
ISSN
0892-6638
eISSN
1530-6860
Page URI
https://pub.uni-bielefeld.de/record/2946513

Zitieren

Aziz P, Haslund-Gourley B, Heithoff D, et al. Altered glycosidase Activities at Physiological pH in the Pathogenesis of Sepsis. In: FASEB JOURNAL. Vol 34. Hoboken: Wiley; 2020.
Aziz, P., Haslund-Gourley, B., Heithoff, D., Westman, J., Restagno, D., Lewis, B., Fried, J., et al. (2020). Altered glycosidase Activities at Physiological pH in the Pathogenesis of Sepsis. FASEB JOURNAL, 34 Hoboken: Wiley. doi:10.1096/fasebj.2020.34.s1.07166
Aziz, P., Haslund-Gourley, B., Heithoff, D., Westman, J., Restagno, D., Lewis, B., Fried, J., Ilse, M. - B., Lübke, T., and Marth, J. (2020). “Altered glycosidase Activities at Physiological pH in the Pathogenesis of Sepsis” in FASEB JOURNAL, vol. 34, (Hoboken: Wiley).
Aziz, P., et al., 2020. Altered glycosidase Activities at Physiological pH in the Pathogenesis of Sepsis. In FASEB JOURNAL. no.34 Hoboken: Wiley.
P. Aziz, et al., “Altered glycosidase Activities at Physiological pH in the Pathogenesis of Sepsis”, FASEB JOURNAL, vol. 34, Hoboken: Wiley, 2020.
Aziz, P., Haslund-Gourley, B., Heithoff, D., Westman, J., Restagno, D., Lewis, B., Fried, J., Ilse, M.-B., Lübke, T., Marth, J.: Altered glycosidase Activities at Physiological pH in the Pathogenesis of Sepsis. FASEB JOURNAL. 34, Wiley, Hoboken (2020).
Aziz, Peter, Haslund-Gourley, Benjamin, Heithoff, Douglas, Westman, Julia, Restagno, Damien, Lewis, Benjamin, Fried, Jeffrey, Ilse, Mai-Britt, Lübke, Torben, and Marth, Jamey. “Altered glycosidase Activities at Physiological pH in the Pathogenesis of Sepsis”. FASEB JOURNAL. Hoboken: Wiley, 2020.Vol. 34.

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