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 | ||||||
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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: |
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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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