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Mast Cell beta-Tryptase Is Enzymatically Stabilized by DNA

Alanazi, Sultan and Grujic, Mirjana and Lampinen, Maria and Rollman, Ola and Sommerhoff, Christian P. and Pejler, Gunnar and Melo, Fabio Rabelo (2020). Mast Cell beta-Tryptase Is Enzymatically Stabilized by DNA. International Journal of Molecular Sciences. 21 , 5065
[Research article]

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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.

Authors/Creators:Alanazi, Sultan and Grujic, Mirjana and Lampinen, Maria and Rollman, Ola and Sommerhoff, Christian P. and Pejler, Gunnar and Melo, Fabio Rabelo
Title:Mast Cell beta-Tryptase Is Enzymatically Stabilized by DNA
Series Name/Journal:International Journal of Molecular Sciences
Year of publishing :2020
Volume:21
Article number:5065
Number of Pages:12
Publisher:MDPI
ISSN:1661-6596
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Cell Biology
Keywords:tryptase, mast cells, DNA, heparin
URN:NBN:urn:nbn:se:slu:epsilon-p-112349
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-112349
Additional ID:
Type of IDID
DOI10.3390/ijms21145065
Web of Science (WoS)000556976500001
ID Code:24553
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: SLUpub Connector
Deposited On:16 Jun 2021 12:16
Metadata Last Modified:16 Jun 2021 12:21

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