Establishment of blood glycosidase activities and their excursions in sepsis.

Autor:	Haslund-Gourley BS; Sanford-Burnham-Prebys Medical Discovery Institute, Infectious and Inflammatory Diseases Center, La Jolla, CA 92037, USA., Aziz PV; Sanford-Burnham-Prebys Medical Discovery Institute, Infectious and Inflammatory Diseases Center, La Jolla, CA 92037, USA., Heithoff DM; Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, CA 93106, USA., Restagno D; Sanford-Burnham-Prebys Medical Discovery Institute, Infectious and Inflammatory Diseases Center, La Jolla, CA 92037, USA., Fried JC; Department of Pulmonary and Critical Care Medicine, Cottage Hospital of Santa Barbara, Santa Barbara, CA 93105, USA., Ilse MB; Department of Chemistry, Biochemistry, Bielefeld University, D-33615, Germany., Bäumges H; Department of Chemistry, Biochemistry, Bielefeld University, D-33615, Germany., Mahan MJ; Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, CA 93106, USA., Lübke T; Department of Chemistry, Biochemistry, Bielefeld University, D-33615, Germany., Marth JD; Sanford-Burnham-Prebys Medical Discovery Institute, Infectious and Inflammatory Diseases Center, La Jolla, CA 92037, USA.
Jazyk:	angličtina
Zdroj:	PNAS nexus [PNAS Nexus] 2022 Jul 11; Vol. 1 (3), pp. pgac113. Date of Electronic Publication: 2022 Jul 11 (Print Publication: 2022).
DOI:	10.1093/pnasnexus/pgac113
Abstrakt:	Glycosidases are hydrolytic enzymes studied principally in the context of intracellular catabolism within the lysosome. Therefore, glycosidase activities are classically measured in experimentally acidified assay conditions reflecting their low pH optima. However, glycosidases are also present in the bloodstream where they may retain sufficient activity to participate in the regulation of glycoprotein half-lives, proteostasis, and disease pathogenesis. We have, herein, established at physiological pH 7.4 in blood plasma and sera the normal ranges of four major glycosidase activities essential for blood glycoprotein remodeling in healthy mice and humans. These activities included β-galactosidase, β-N-acetylglucosaminidase, α-mannosidase, and α-fucosidase. We have identified their origins to include the mammalian genes Glb1, HexB, Man2a1 , and Fuca1 . In experimental sepsis, excursions of glycosidase activities occurred with differences in host responses to discrete bacterial pathogens. Among similar excursions in human sepsis, the elevation of β-galactosidase activity was a prognostic indicator of increased likelihood of patient death. (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)
Databáze:	MEDLINE
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