{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:10:57Z","timestamp":1792033857474,"version":"4.4.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,8,14]]},"abstract":"<jats:p>\n                    In vivo recycling of nitrate (NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) and nitrite (NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) is an important alternative pathway for the generation of nitric oxide (NO) and maintenance of systemic nitrate\u2013nitrite\u2013NO balance. More than 25% of the circulating NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    is actively removed and secreted by salivary glands. Oral commensal bacteria convert salivary NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    to NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    , which enters circulation and leads to NO generation. The transporters for NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    in salivary glands have not yet been identified. Here we report that sialin (\n                    <jats:italic>SLC17A<\/jats:italic>\n                    <jats:italic>5<\/jats:italic>\n                    ), mutations in which cause Salla disease and infantile sialic acid storage disorder (ISSD), functions as an electrogenic 2NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    cotransporter in the plasma membrane of salivary gland acinar cells. We have identified an extracellular pH-dependent anion current that is carried by NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    or sialic acid (SA), but not by Br\n                    <jats:sup>\u2212<\/jats:sup>\n                    , and is accompanied by intracellular acidification. Both responses were reduced by knockdown of sialin expression and increased by the plasma membrane-targeted sialin mutant (L22A-L23A). Fibroblasts from patients with ISSD displayed reduced SA- and NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    -induced currents compared with healthy controls. Furthermore, expression of disease-associated sialin mutants in fibroblasts and salivary gland cells suppressed the H\n                    <jats:sup>+<\/jats:sup>\n                    -dependent NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    conductance. Importantly, adenovirus-dependent expression of the sialinH183R mutant in vivo in pig salivary glands decreased NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    secretion in saliva after intake of a NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    -rich diet. Taken together, these data demonstrate that sialin mediates nitrate influx into salivary gland and other cell types. We suggest that the 2NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    transport function of sialin in salivary glands can contribute significantly to clearance of serum nitrate, as well as nitrate recycling and physiological nitrite-NO homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1116633109","type":"journal-article","created":{"date-parts":[[2012,7,10]],"date-time":"2012-07-10T07:59:01Z","timestamp":1341907141000},"page":"13434-13439","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":207,"title":["Sialin (\n                    <i>SLC17A5<\/i>\n                    ) functions as a nitrate transporter in the plasma membrane"],"prefix":"10.1073","volume":"109","author":[{"given":"Lizheng","family":"Qin","sequence":"first","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xibao","family":"Liu","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifei","family":"Sun","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Fan","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengsheng","family":"Xia","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Ding","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwei Ling","family":"Ong","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Adams","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senrong","family":"Qi","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyuan","family":"Jin","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liankun","family":"Gu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing 100142, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dajun","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing 100142, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indu S.","family":"Ambudkar","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of 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