Oxygen sensing in the circulation: "cross talk" between red blood cells and the vasculature.
Oxygen (O(2)) sensing in blood and regulation of microvascular tone appear to involve hemoglobin (Hb) conformational changes resulting from O(2) desaturation. This observation has prompted the thought that Hb functions as both an O(2) sensor and regulator of microvasular blood flow to meet local tissue oxygen demand. The mechanism(s) by which this is accomplished has recently been the subject of increasing debate. Three primary hypotheses are described within the literature and include release of adenosine 5'-triphosphate by red blood cells (RBCs), release of S-nitrosylated molecules from RBCs originally bound to beta93 cysteine residues of oxyHb, and nitrite conversion and storage of nitric oxide by Hb at the site of ferric (Fe(3+)) and ferrous (Fe(2+)) Hb. Within extravascular cells, the global regulator of oxygen homeostasis is hypoxia-inducible factor-1 (HIF- 1). This transcriptional factor is tightly regulated by O(2) and cellular redox-sensitive mechanisms. HIF-1 activation is responsible for the up-regulation of proteins, which increase O(2) supply. We believe that there are important and yet unexplored mechanisms by which RBCs can directly or indirectly communicate via redox intermediates with extravascular sites as part of the global O(2) sensing mechanism.
Buehler
Paul W
PW
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.
Alayash
Abdu I
AI
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D004912:Erythrocytes / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007501:Iron / Q000737:chemistry; D008954:Models, Biological; D008956:Models, Chemical; D009569:Nitric Oxide / Q000737:chemistry; D010100:Oxygen / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
C497442:HIF1A protein, human; D006454:Hemoglobins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D007501:Iron; D010100:Oxygen