{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T21:17:49Z","timestamp":1780694269671,"version":"3.54.1"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The binding of nitric oxide (NO) to heme in the \u03b21 subunit of soluble guanylyl cyclase (sGC) activates both the heterodimeric \u03b11\u03b21 and \u03b12\u03b21 isoforms of the enzyme, leading to the increased production of cGMP from GTP. In cultured human mast cells, exogenous NO is able to inhibit mast cell degranulation via NO-cGMP signaling. However, under inflammatory oxidative or nitrosative stress, sGC becomes insensitive to NO. The occurrence of mast cells in healthy and inflamed human tissues and the in vivo expression of the \u03b11 and \u03b21 subunits of sGC in human mast cells during inflammation remain largely unresolved and were investigated here. Using peroxidase and double immunohistochemical incubations, no mast cells were found in healthy dental pulp, whereas the inflammation of dental pulp initiated the occurrence of several mast cells expressing the \u03b11 and \u03b21 subunits of sGC. Since inflammation-induced oxidative and nitrosative stress oxidizes Fe2+ to Fe3+ in the \u03b21 subunit of sGC, leading to the desensitization of sGC to NO, we hypothesize that the NO- and heme-independent pharmacological activation of sGC in mast cells may be considered as a regulatory strategy for mast cell functions in inflamed human dental pulp.<\/jats:p>","DOI":"10.3390\/ijms24020901","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T04:28:17Z","timestamp":1672806497000},"page":"901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dental Pulp Inflammation Initiates the Occurrence of Mast Cells Expressing the \u03b11 and \u03b21 Subunits of Soluble Guanylyl Cyclase"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-9942","authenticated-orcid":false,"given":"Y\u00fcksel","family":"Korkmaz","sequence":"first","affiliation":[{"name":"Department of Periodontology and Operative Dentistry, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Plomann","sequence":"additional","affiliation":[{"name":"Center for Biochemistry, Faculty of Medicine, University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behrus","family":"Puladi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital RWTH Aachen, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayseg\u00fcl","family":"Demirbas","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry, Faculty of Dentistry, Mugla S\u0131tk\u0131 Kocman University, Mugla 48000, Turkey"},{"name":"Department of Restorative Dentistry, Faculty of Dentistry, Ege University, Izmir 35040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Bloch","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, 50933 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Deschner","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Operative Dentistry, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1161\/01.RES.0000082524.34487.31","article-title":"Regulation of nitric oxide-sensitive guanylyl cyclase","volume":"93","author":"Friebe","year":"2003","journal-title":"Circ. 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