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Research article - Peer-reviewed, 2020

Mast Cell beta-Tryptase Is Enzymatically Stabilized by DNA

Alanazi, Sultan; Grujic, Mirjana; Lampinen, Maria; Rollman, Ola; Sommerhoff, Christian P.; Pejler, Gunnar; Melo, Fabio Rabelo;

Abstract

Tryptase is a tetrameric serine protease located within the secretory granules of mast cells. In the secretory granules, tryptase is stored in complex with negatively charged heparin proteoglycans and it is known that heparin is essential for stabilizing the enzymatic activity of tryptase. However, recent findings suggest that enzymatically active tryptase also can be found in the nucleus of murine mast cells, but it is not known how the enzmatic activity of tryptase is maintained in the nuclear milieu. Here we hypothesized that tryptase, as well as being stabilized by heparin, can be stabilized by DNA, the rationale being that the anionic charge of DNA could potentially substitute for that of heparin to execute this function. Indeed, we showed that double-stranded DNA preserved the enzymatic activity of human beta-tryptase with a similar efficiency as heparin. In contrast, single-stranded DNA did not have this capacity. We also demonstrated that DNA fragments down to 400 base pairs have tryptase-stabilizing effects equal to that of intact DNA. Further, we showed that DNA-stabilized tryptase was more efficient in degrading nuclear core histones than heparin-stabilized enzyme. Finally, we demonstrated that tryptase, similar to its nuclear localization in murine mast cells, is found within the nucleus of primary human skin mast cells. Altogether, these finding reveal a hitherto unknown mechanism for the stabilization of mast cell tryptase, and these findings can have an important impact on our understanding of how tryptase regulates nuclear events.

Keywords

tryptase; mast cells; DNA; heparin

Published in

International Journal of Molecular Sciences

2020, volume: 21, number: 14, article number: 5065
Publisher: MDPI

Authors' information

Alanazi, Sultan
Uppsala University
Grujic, Mirjana
Uppsala University
Lampinen, Maria
Uppsala University
Rollman, Ola
Uppsala University
Sommerhoff, Christian P.
University of Munich
Uppsala University
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)
Melo, Fabio Rabelo
Uppsala University

UKÄ Subject classification

Cell Biology

Publication Identifiers

DOI: https://doi.org/10.3390/ijms21145065

URI (permanent link to this page)

https://res.slu.se/id/publ/112349