Mast Cell β-Tryptase Is Enzymatically Stabilized by DNA

International Journal of Molecular Sciences

Mirjana Grujic¹  Sultan Alanazi¹  Maria Lampinen¹  Gunnar Pejler¹  FabioRabelo Melo¹  Ola Rollman²  ChristianP. Sommerhoff³ 

[1] Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden;Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden;Institute of Laboratory Medicine, University Hospital, 80539 LMU Munich, Germany;

关键词: tryptase;    mast cells;    DNA;    heparin;   

DOI  :  10.3390/ijms21145065

来源: DOAJ

【 摘 要 】

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 β-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.

【 授权许可】

Unknown