Disease relevance of Eraf

• The alpha-Hb-stabilizing protein (AHSP) is an erythroid protein that specifically binds alpha-Hb and prevents its precipitation in vitro, which suggests that it may function to limit free alpha-Hb toxicities in vivo [1].
• Our findings raise the possibility that altered AHSP expression levels could modulate the severity of beta-thalassemia in humans [1].
• By using this assay, the production of an EDRF-like activity in homogenates and cytosolic fractions of N1E-115 neuroblastoma cells was observed [2].
• Since endothelial cells do not require this additional arginine transport to produce NO, we reasoned that a competitive inhibitor of cytokine-inducible L-arginine transport would not inhibit EDRF activity in blood vessels, and thus might be effectively employed against endotoxic shock [3].
• However, during and following ischemia there may be loss of this NOS or inability to mobilize a storage form of the EDRF, which it produces [4].

High impact information on Eraf

• In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation [5].
• Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied [5].
• Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine [5].
• Nitric oxide (NO), a potent vasodilator produced by endothelial cells, is thought to be the endothelium-dependent relaxing factor (EDRF) which mediates vascular relaxation in response to acetylcholine, bradykinin and substance P in many vascular beds [6].
• Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates beta-thalassemia [1].

Chemical compound and disease context of Eraf

• The effects of EDRF/NO releasers or calcium ionophore A23187 on cyanide toxicity in mice [7].

Biological context of Eraf

• Finally, loss of AHSP worsened the phenotype of beta-thalassemia, a common inherited anemia characterized by excess free alpha-Hb [1].
• Stimulation of the release of endothelium-derived relaxing factor (EDRF) in the kidney has been shown to result in natriuresis without affecting glomerular filtration rate [8].
• Since cGMP is the second messenger of EDRF in vascular smooth muscle, we measured the effects of Bk on cGMP production in M-1 cells in the presence and absence of CPAE cells [8].
• BACKGROUND AND PURPOSE: Tetrahydrobiopterin (THBP) is an essential cofactor for nitric oxide synthase (NOS), which is responsible for the synthesis of the endothelium-derived relaxing factor (EDRF) responsible for mediating the vasorelaxation produced by acetylcholine (ACh) [9].

Anatomical context of Eraf

• The AHSP promoter was transactivated by EKLF in K562 cells, which lack EKLF [10].
• Production of an EDRF-like activity in the cytosol of N1E-115 neuroblastoma cells [2].
• Receptor-mediated generation of an EDRF-like intermediate in a neuronal cell line detected by spin trapping techniques [11].
• Agents that modify EDRF formation alter antiplatelet properties of brain arteriolar endothelium in vivo [12].

Associations of Eraf with chemical compounds

• Nitroarginine (N-Arg, 10(-4) M), a competitive inhibitor of EDRF production, blocked the inhibition in M-1 Isc due to both agonists [8].
• Production of the EDRF-like factor was dependent on L-arginine and NADPH [2].
• We conclude that the dilating effects of thimerosal on diameter require two endothelium-derived agents: EDRF and one or more prostaglandins acting in concert [13].
• Dilation was also eliminated by topical L-NMMA, a reported inhibitor of EDRF synthesis [13].
• It has been proposed that NH2OH is a putative intermediate in the biochemical pathway for the generation of nitric oxide (NO)/endothelium-derived relaxing factor (EDRF) from L-arginine [14].

Analytical, diagnostic and therapeutic context of Eraf

• One such compound (CNI-1493) was studied further in animal models of endothelial-derived relaxing factor (EDRF) activity, carrageenan inflammation, and lethal lipopolysaccharide (LPS) challenge [3].
• To this end isolated mouse renal juxtaglomerular cells were cocultured with bovine aortic endothelial cells which produced and released significant amounts of EDRF as assayed by guanylate cyclase activities which were measured separately in endothelial and juxtaglomerular cells as well as in the cocultures of juxtaglomerular with endothelial cells [15].
• The enriched diet did not affect constriction produced by topically applied NG-monomethyl-L-arginine, an inhibitor of the synthesis of endothelium-derived relaxing factor (EDRF) [16].

References