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Gene Review

Ahsp  -  alpha hemoglobin stabilizing protein

Mus musculus

Synonyms: Alpha-hemoglobin-stabilizing protein, EDRF, Edrf, Eraf, Erythroid differentiation-related factor, ...
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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


Chemical compound and disease context of Eraf


Biological context of Eraf


Anatomical context of Eraf


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].


  1. Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates beta-thalassemia. Kong, Y., Zhou, S., Kihm, A.J., Katein, A.M., Yu, X., Gell, D.A., Mackay, J.P., Adachi, K., Foster-Brown, L., Louden, C.S., Gow, A.J., Weiss, M.J. J. Clin. Invest. (2004) [Pubmed]
  2. Production of an EDRF-like activity in the cytosol of N1E-115 neuroblastoma cells. Gorsky, L.D., Förstermann, U., Ishii, K., Murad, F. FASEB J. (1990) [Pubmed]
  3. An inhibitor of macrophage arginine transport and nitric oxide production (CNI-1493) prevents acute inflammation and endotoxin lethality. Bianchi, M., Ulrich, P., Bloom, O., Meistrell, M., Zimmerman, G.A., Schmidtmayerova, H., Bukrinsky, M., Donnelley, T., Bucala, R., Sherry, B. Mol. Med. (1995) [Pubmed]
  4. A review of vasomotor responses of arterioles on the surface of the mouse brain: the necessary prelude to studies using genetically manipulated mice. Rosenblum, W.I. Microcirculation (New York, N.Y. : 1994) (1998) [Pubmed]
  5. Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin. Feng, L., Gell, D.A., Zhou, S., Gu, L., Kong, Y., Li, J., Hu, M., Yan, N., Lee, C., Rich, A.M., Armstrong, R.S., Lay, P.A., Gow, A.J., Weiss, M.J., Mackay, J.P., Shi, Y. Cell (2004) [Pubmed]
  6. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Huang, P.L., Huang, Z., Mashimo, H., Bloch, K.D., Moskowitz, M.A., Bevan, J.A., Fishman, M.C. Nature (1995) [Pubmed]
  7. The effects of EDRF/NO releasers or calcium ionophore A23187 on cyanide toxicity in mice. Baskin, S.I., Nealley, E.W., Lempka, J.C. Toxicol. Appl. Pharmacol. (1996) [Pubmed]
  8. Endothelium-derived relaxing factor inhibits transport and increases cGMP content in cultured mouse cortical collecting duct cells. Stoos, B.A., Carretero, O.A., Farhy, R.D., Scicli, G., Garvin, J.L. J. Clin. Invest. (1992) [Pubmed]
  9. Tetrahydrobiopterin, a cofactor for nitric oxide synthase, produces endothelium-dependent dilation of mouse pial arterioles. Rosenblum, W.I. Stroke (1997) [Pubmed]
  10. Alterations in expression and chromatin configuration of the alpha hemoglobin-stabilizing protein gene in erythroid Kruppel-like factor-deficient mice. Pilon, A.M., Nilson, D.G., Zhou, D., Sangerman, J., Townes, T.M., Bodine, D.M., Gallagher, P.G. Mol. Cell. Biol. (2006) [Pubmed]
  11. Receptor-mediated generation of an EDRF-like intermediate in a neuronal cell line detected by spin trapping techniques. Arroyo, C.M., Forray, C., el-Fakahany, E.E., Rosen, G.M. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  12. Agents that modify EDRF formation alter antiplatelet properties of brain arteriolar endothelium in vivo. Nishimura, H., Rosenblum, W.I., Nelson, G.H., Boynton, S. Am. J. Physiol. (1991) [Pubmed]
  13. The endothelium-dependent effects of thimerosal on mouse pial arterioles in vivo: evidence for control of microvascular events by EDRF as well as prostaglandins. Rosenblum, W.I., Nishimura, H., Ellis, E.F., Nelson, G.H. J. Cereb. Blood Flow Metab. (1992) [Pubmed]
  14. N-hydroxylamine is not an intermediate in the conversion of L-arginine to an activator of soluble guanylate cyclase in neuroblastoma N1E-115 cells. Pou, S., Pou, W.S., Rosen, G.M., el-Fakahany, E.E. Biochem. J. (1991) [Pubmed]
  15. Effect of endothelium-derived relaxing factor on renin secretion from isolated mouse renal juxtaglomerular cells. Schricker, K., Ritthaler, T., Krämer, B.K., Kurtz, A. Acta Physiol. Scand. (1993) [Pubmed]
  16. Vitamin E ameliorates adverse effects of endothelial injury in brain arterioles. Rosenblum, W.I., Nelson, G.H., Bei, R.A., Brandt, R.B., Chan, W. Am. J. Physiol. (1996) [Pubmed]
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