title: Effects of carbon monoxide (CO) delivery by a CO donor or hemoglobin on vascular hypoxia inducible factor 1α and mitochondrial respiration.
abstract: We examined carbon monoxide (CO) delivery by carbon monoxide-releasing molecule 2 (CORM-2) or hemoglobin (Hb) on cellular oxygen sensing and mitochondrial respiration in bovine aortic endothelial cells (BAECs). CORM-2 reduced hypoxia-inducible factor-1α (HIF-1α) and endothelin-1 (ET-1) expression in normoxic and hypoxic cells, but while Hb alone significantly reduced HIF-1α stabilization in hypoxic cells, CO delivered by Hb (Hb-CO) had no effect on HIF-1α stabilization. CO dose-dependently increased basal oxygen consumption and reduced overall mitochondrial respiratory capacity. Hb-CO increased basal oxygen consumption but did not alter respiratory capacity. Together, CO reduced ET-1, and, at low doses, had no effect on endothelial mitochondria oxygen consumption. CO ligation to Hb may be developed further as non-vasoactive oxygen therapeutic without compromising mitochondrial function.
authors: Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration (FDA), Bethesda, MD 20892, United States.
authors: Chad E N
authors: CE
authors: Reiter
authors: Abdu I
authors: AI
authors: Alayash
keywords: BAEC, bovine aortic endothelial cells; CO, carbon monoxide; CORM-2, CO-releasing molecule-2; Carbon monoxide; ET-1, endothelin-1; HBOC, Hb-based oxygen carrier; HIF-1α, hypoxia-inducible factor 1α; Hb, hemoglobin; Hb-CO, hemoglobin-ligated with CO; Hemoglobin; Hypoxia-inducible factor; Mitochondria; NO, nitric oxide; OCR, oxygen consumption rate; PHD-2, proline hydroxylase-2
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