Redox-Regulation of α-Globin in Vascular Physiology
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 reactio...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/1/159 |
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| author | Laurent Kiger Julia Keith Abdullah Freiwan Alfonso G. Fernandez Heather Tillman Brant E. Isakson Mitchell J. Weiss Christophe Lechauve |
| author_facet | Laurent Kiger Julia Keith Abdullah Freiwan Alfonso G. Fernandez Heather Tillman Brant E. Isakson Mitchell J. Weiss Christophe Lechauve |
| author_sort | Laurent Kiger |
| collection | DOAJ |
| description | 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 α-globin, which causes vasoconstriction by degrading NO. This reaction converts reduced (Fe<sup>2+</sup>) α-globin to the oxidized (Fe<sup>3+</sup>) form, which is unstable, cytotoxic, and unable to degrade NO. Therefore, (Fe<sup>3+</sup>) α-globin must be stabilized and recycled to (Fe<sup>2+</sup>) α-globin to reinitiate the catalytic cycle. The molecular chaperone α-hemoglobin-stabilizing protein (AHSP) binds (Fe<sup>3+</sup>) α-globin to inhibit its degradation and facilitate its reduction. The mechanisms that reduce (Fe<sup>3+</sup>) α-globin in ECs are unknown, although endothelial nitric oxide synthase (eNOS) and cytochrome <i>b</i><sub>5</sub> reductase (CyB5R3) with cytochrome <i>b</i><sub>5</sub> type A (CyB5a) can reduce (Fe<sup>3+</sup>) α-globin in solution. Here, we examine the expression and cellular localization of eNOS, CyB5a, and CyB5R3 in mouse arterial ECs and show that α-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. |
| first_indexed | 2024-03-10T01:59:50Z |
| format | Article |
| id | doaj.art-7342d090c6d2456abfab3e5b28021b3b |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T01:59:50Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-7342d090c6d2456abfab3e5b28021b3b2023-11-23T12:48:16ZengMDPI AGAntioxidants2076-39212022-01-0111115910.3390/antiox11010159Redox-Regulation of α-Globin in Vascular PhysiologyLaurent Kiger0Julia Keith1Abdullah Freiwan2Alfonso G. Fernandez3Heather Tillman4Brant E. Isakson5Mitchell J. Weiss6Christophe Lechauve7Inserm U955, Institut Mondor de Recherche Biomédicale, University Paris Est Creteil, 94017 Créteil, FranceDepartment of Hematology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Hematology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USARobert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USADepartment of Hematology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Hematology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USAInterest 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 α-globin, which causes vasoconstriction by degrading NO. This reaction converts reduced (Fe<sup>2+</sup>) α-globin to the oxidized (Fe<sup>3+</sup>) form, which is unstable, cytotoxic, and unable to degrade NO. Therefore, (Fe<sup>3+</sup>) α-globin must be stabilized and recycled to (Fe<sup>2+</sup>) α-globin to reinitiate the catalytic cycle. The molecular chaperone α-hemoglobin-stabilizing protein (AHSP) binds (Fe<sup>3+</sup>) α-globin to inhibit its degradation and facilitate its reduction. The mechanisms that reduce (Fe<sup>3+</sup>) α-globin in ECs are unknown, although endothelial nitric oxide synthase (eNOS) and cytochrome <i>b</i><sub>5</sub> reductase (CyB5R3) with cytochrome <i>b</i><sub>5</sub> type A (CyB5a) can reduce (Fe<sup>3+</sup>) α-globin in solution. Here, we examine the expression and cellular localization of eNOS, CyB5a, and CyB5R3 in mouse arterial ECs and show that α-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.https://www.mdpi.com/2076-3921/11/1/159α-globinendothelial nitric oxide synthase (eNOS)cytochromeredox systemarteriesblood pressure |
| spellingShingle | Laurent Kiger Julia Keith Abdullah Freiwan Alfonso G. Fernandez Heather Tillman Brant E. Isakson Mitchell J. Weiss Christophe Lechauve Redox-Regulation of α-Globin in Vascular Physiology Antioxidants α-globin endothelial nitric oxide synthase (eNOS) cytochrome redox system arteries blood pressure |
| title | Redox-Regulation of α-Globin in Vascular Physiology |
| title_full | Redox-Regulation of α-Globin in Vascular Physiology |
| title_fullStr | Redox-Regulation of α-Globin in Vascular Physiology |
| title_full_unstemmed | Redox-Regulation of α-Globin in Vascular Physiology |
| title_short | Redox-Regulation of α-Globin in Vascular Physiology |
| title_sort | redox regulation of α globin in vascular physiology |
| topic | α-globin endothelial nitric oxide synthase (eNOS) cytochrome redox system arteries blood pressure |
| url | https://www.mdpi.com/2076-3921/11/1/159 |
| work_keys_str_mv | AT laurentkiger redoxregulationofaglobininvascularphysiology AT juliakeith redoxregulationofaglobininvascularphysiology AT abdullahfreiwan redoxregulationofaglobininvascularphysiology AT alfonsogfernandez redoxregulationofaglobininvascularphysiology AT heathertillman redoxregulationofaglobininvascularphysiology AT branteisakson redoxregulationofaglobininvascularphysiology AT mitchelljweiss redoxregulationofaglobininvascularphysiology AT christophelechauve redoxregulationofaglobininvascularphysiology |