Crawford 2006 Blood: Difference between revisions
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{{Publication | {{Publication | ||
|title=Crawford JH, Isbell TS, Huang Z, Shiva S, Chacko BK, Schechter AN, Darley-Usmar VM, Kerby JD, Lang JD Jr, Kraus D, Ho C, Gladwin MT, Patel RP (2006) Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood 107: 566- | |title=Crawford JH, Isbell TS, Huang Z, Shiva S, Chacko BK, Schechter AN, Darley-Usmar VM, Kerby JD, Lang JD Jr, Kraus D, Ho C, Gladwin MT, Patel RP (2006) Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood 107:566-74. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/16195332 PMID:16195332 ] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/16195332 PMID: 16195332 Open Access] | ||
|authors=Crawford JH, Isbell TS, Huang | |authors=Crawford JH, Isbell TS, Huang Zhi, Shiva S, Chacko BK, Schechter AN, Darley-Usmar VM, Kerby JD, Lang JD Jr, Kraus D, Ho C, Gladwin MT, Patel RP | ||
|year=2006 | |year=2006 | ||
|journal=Blood | |journal=Blood | ||
|abstract=Local vasodilation in response to hypoxia is a fundamental physiologic response | |abstract=Local vasodilation in response to hypoxia is a fundamental physiologic response | ||
ensuring oxygen delivery to tissues under metabolic stress. Recent studies identify a role for the red blood cell (RBC), with hemoglobin the hypoxic sensor. Herein, we investigate the mechanisms regulating this process and explore the relative roles of adenosine triphosphate, S-nitrosohemoglobin, and nitrite as effectors. We provide evidence that hypoxic RBCs mediate vasodilation by reducing nitrite to nitric oxide (NO) and ATP release. | ensuring oxygen delivery to tissues under metabolic stress. Recent studies identify a role for the red blood cell (RBC), with hemoglobin the hypoxic sensor. Herein, we investigate the mechanisms regulating this process and explore the relative roles of adenosine triphosphate, S-nitrosohemoglobin, and nitrite as effectors. We provide evidence that hypoxic RBCs mediate vasodilation by reducing nitrite to nitric oxide (NO) and ATP release. | ||
NO dependence for nitrite-mediated vasodilation was evidenced by NO gas formation, stimulation of cGMP production, and inhibition of mitochondrial respiration in a process sensitive to the NO scavenger C-PTIO. The nitrite reductase activity of hemoglobin is modulated by heme deoxygenation and heme redox potential, with maximal activity observed at 50% hemoglobin oxygenation ( | NO dependence for nitrite-mediated vasodilation was evidenced by NO gas formation, stimulation of cGMP production, and inhibition of mitochondrial respiration in a process sensitive to the NO scavenger C-PTIO. The nitrite reductase activity of hemoglobin is modulated by heme deoxygenation and heme redox potential, with maximal activity observed at 50% hemoglobin oxygenation (''p''<sub>50</sub>). Concomitantly, vasodilation is initiated at the ''p''<sub>50</sub>, suggesting that oxygen sensing by hemoglobin is mechanistically linked to nitrite reduction and stimulation ofvasodilation. Mutation of the conserved Ξ²93cys residue decreases the heme redox potential (ie, decreases E1/2), an effect that increases nitrite reductase activity and vasodilation at any given hemoglobin saturation. These data support a function for RBC hemoglobin as an allosterically and redox-regulated nitrite reductase whose βenzyme activityβ couples hypoxia to increased NO-dependent blood flow. | ||
|mipnetlab=US AL Birmingham Kraus DW | |mipnetlab=US AL Birmingham Kraus DW | ||
|discipline=Biomedicine | |discipline=Biomedicine | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, Genetic knockout;overexpression | |||
|organism=Rat | |||
|tissues=Blood cells | |||
|preparations=Isolated mitochondria | |||
|injuries=Ischemia-reperfusion, Oxidative stress;RONS | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|discipline=Biomedicine | |discipline=Biomedicine | ||
}} | }} |
Latest revision as of 08:52, 17 August 2022
Crawford JH, Isbell TS, Huang Z, Shiva S, Chacko BK, Schechter AN, Darley-Usmar VM, Kerby JD, Lang JD Jr, Kraus D, Ho C, Gladwin MT, Patel RP (2006) Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood 107:566-74. |
Crawford JH, Isbell TS, Huang Zhi, Shiva S, Chacko BK, Schechter AN, Darley-Usmar VM, Kerby JD, Lang JD Jr, Kraus D, Ho C, Gladwin MT, Patel RP (2006) Blood
Abstract: Local vasodilation in response to hypoxia is a fundamental physiologic response ensuring oxygen delivery to tissues under metabolic stress. Recent studies identify a role for the red blood cell (RBC), with hemoglobin the hypoxic sensor. Herein, we investigate the mechanisms regulating this process and explore the relative roles of adenosine triphosphate, S-nitrosohemoglobin, and nitrite as effectors. We provide evidence that hypoxic RBCs mediate vasodilation by reducing nitrite to nitric oxide (NO) and ATP release. NO dependence for nitrite-mediated vasodilation was evidenced by NO gas formation, stimulation of cGMP production, and inhibition of mitochondrial respiration in a process sensitive to the NO scavenger C-PTIO. The nitrite reductase activity of hemoglobin is modulated by heme deoxygenation and heme redox potential, with maximal activity observed at 50% hemoglobin oxygenation (p50). Concomitantly, vasodilation is initiated at the p50, suggesting that oxygen sensing by hemoglobin is mechanistically linked to nitrite reduction and stimulation ofvasodilation. Mutation of the conserved Ξ²93cys residue decreases the heme redox potential (ie, decreases E1/2), an effect that increases nitrite reductase activity and vasodilation at any given hemoglobin saturation. These data support a function for RBC hemoglobin as an allosterically and redox-regulated nitrite reductase whose βenzyme activityβ couples hypoxia to increased NO-dependent blood flow.
β’ O2k-Network Lab: US AL Birmingham Kraus DW
Labels: MiParea: Respiration, Genetic knockout;overexpression
Stress:Ischemia-reperfusion, Oxidative stress;RONS Organism: Rat Tissue;cell: Blood cells Preparation: Isolated mitochondria
HRR: Oxygraph-2k