{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:19:24Z","timestamp":1792120764600,"version":"4.4.0"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01 DK61692"],"award-info":[{"award-number":["R01 DK61692"]}]},{"name":"National Institute of Health","award":["R01 HL088554"],"award-info":[{"award-number":["R01 HL088554"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["5POST25870017"],"award-info":[{"award-number":["5POST25870017"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Interest in the structure, function, and evolutionary relations of circulating and intracellular globins dates back more than 60 years to the first determination of the three-dimensional structure of these proteins. Non-erythrocytic globins have been implicated in circulatory control through reactions that couple nitric oxide (NO) signaling with cellular oxygen availability and redox status. Small artery endothelial cells (ECs) express free \u03b1-globin, which causes vasoconstriction by degrading NO. This reaction converts reduced (Fe2+) \u03b1-globin to the oxidized (Fe3+) form, which is unstable, cytotoxic, and unable to degrade NO. Therefore, (Fe3+) \u03b1-globin must be stabilized and recycled to (Fe2+) \u03b1-globin to reinitiate the catalytic cycle. The molecular chaperone \u03b1-hemoglobin-stabilizing protein (AHSP) binds (Fe3+) \u03b1-globin to inhibit its degradation and facilitate its reduction. The mechanisms that reduce (Fe3+) \u03b1-globin in ECs are unknown, although endothelial nitric oxide synthase (eNOS) and cytochrome b5 reductase (CyB5R3) with cytochrome b5 type A (CyB5a) can reduce (Fe3+) \u03b1-globin in solution. Here, we examine the expression and cellular localization of eNOS, CyB5a, and CyB5R3 in mouse arterial ECs and show that \u03b1-globin can be reduced by either of two independent redox systems, CyB5R3\/CyB5a and eNOS. Together, our findings provide new insights into the regulation of blood vessel contractility.<\/jats:p>","DOI":"10.3390\/antiox11010159","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T12:34:04Z","timestamp":1642163644000},"page":"159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Redox-Regulation of \u03b1-Globin in Vascular Physiology"],"prefix":"10.3390","volume":"11","author":[{"given":"Laurent","family":"Kiger","sequence":"first","affiliation":[{"name":"Inserm U955, Institut Mondor de Recherche Biom\u00e9dicale, University Paris Est Creteil, 94017 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Keith","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Freiwan","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso G.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Tillman","sequence":"additional","affiliation":[{"name":"Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brant E.","family":"Isakson","sequence":"additional","affiliation":[{"name":"Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell J.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2179-6856","authenticated-orcid":false,"given":"Christophe","family":"Lechauve","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6675","DOI":"10.1073\/pnas.0308657101","article-title":"Ancestral hemoglobins in Archaea","volume":"101","author":"Freitas","year":"2004","journal-title":"Proc. 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