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AHSP  -  alpha hemoglobin stabilizing protein

Homo sapiens

Synonyms: Alpha-hemoglobin-stabilizing protein, EDRF, ERAF, Erythroid differentiation-related factor, Erythroid-associated factor
 
 
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Disease relevance of ERAF

 

Psychiatry related information on ERAF

  • EDRF transcripts and diagnosis of variant Creutzfeldt-Jakob disease [5].
  • OBJECTIVES: to provide data and detect possible differences in self-assessment of appetite, hunger feelings and sensory perception in different health group of elderly using the Appetite, Hunger feelings and Sensory Perception (AHSP) questionnaire [6].
 

High impact information on ERAF

 

Chemical compound and disease context of ERAF

  • Therefore, we investigated whether acetylcholine releases EDRF in humans in vivo and, if so, whether the response altered in essential hypertension [8].
  • Nitroglycerin (NTG), frequently utilized in the management of unstable angina pectoris and acute myocardial infarction, undergoes bioconversion, via a sulfhydryl-dependent process, to nitric oxide, which is identical or closely related to EDRF [9].
  • The release of EDRF from the endothelium can be mediated by both pertussis toxin-sensitive (alpha 2-adrenoceptor activation, serotonin, aggregating platelets, leukotrienes) and insensitive (adenosine diphosphate (ADP), bradykinin) G proteins [10].
  • The antiaggregatory effect of EDRF is synergistic with prostacyclin, so their combined release may represent a physiological mechanism aimed at preventing thrombus formation [11].
  • Hence, impairment of EDRF release or function could contribute to the reduced placental blood flow observed in various disease states associated with increased thromboxane A2 production such as pre-eclampsia [12].
 

Biological context of ERAF

 

Anatomical context of ERAF

  • Folding in the endoplasmic reticulum (ER) must couple protein-synthesis pathways operating outside of the compartment with ER-assisted folding (ERAF) pathways in the lumen [15].
  • The alpha-hemoglobin-stabilizing protein (AHSP), a small protein of 102 amino acids, is synthesized in red blood cell precursors [16].
  • Because AHSP might act as a chaperone to prevent the harmful aggregation of alpha-globin during normal erythroid cell development and in diseases of globin chain imbalance, it is important to characterize the biochemical properties of the AHSP.alpha-globin complex [13].
  • He then recounts how an accidental finding in an experiment in 1978 on preparations of rabbit aorta eventually led to the discovery of endothelium dependent relaxation and the endothelium-derived relaxing factor (EDRF); and how additional findings led him to propose in 1986 that EDRF is nitric oxide [17].
  • The discovery of endothelium-derived relaxing factor (EDRF) and its importance in the identification of nitric oxide (NO) originated with studies using rabbit aorta to examine drug-receptor interactions in vascular smooth muscle [18].
 

Associations of ERAF with chemical compounds

  • In vitro the binding of AHSP to ferrous alpha-Hb accelerates oxidation of the heme iron in alpha-Hb, but the complex is more resistant to protein unfolding [14].
  • Results obtained with recombinant Groene Hart alpha-Hb and Diamant alpha-Hb, in which proline 119 is replaced by a serine and a leucine, respectively, showed clearly an impaired interaction with AHSP [14].
  • Bradykinin caused concentration-dependent release of NO from the cells in amounts sufficient to account for the biological activity of EDRF [19].
  • Smooth muscle relaxation by acetylcholine and a number of other agonists was found to be dependent on the presence of endothelial cells, which, when stimulated by the agonist, released a diffusable, very labile, nonprostanoid substance, termed EDRF, that acted on vascular smooth muscle cells to activate relaxation [18].
  • By contrast, brief (15 min) exposure of endothelial cells, stimulated to secrete EDRF, to homocysteine results in the formation of S-NO-homocysteine, a potent antiplatelet agent and vasodilator [20].
 

Other interactions of ERAF

 

Analytical, diagnostic and therapeutic context of ERAF

  • CONCLUSION: A strategy of approximately 24-hour delay in cardioversion shock timing decreased the incidence of ERAF, relative to a shock delivered within a few hours of AF onset [21].
  • We have used isothermal titration calorimetry to show that the interaction is of moderate affinity with an association constant of 1 x 10(7) m(-1) and is thus likely to be biologically significant given the concentration of AHSP (approximately 0.1 mm) and hemoglobin (approximately 4 mm) in the late pro-erythroblast [13].
  • AHSP and alpha-globin are both monomeric in solution as determined by analytical ultracentrifugation and bind each other to form a complex with 1:1 subunit stoichiometry, as judged by gel filtration and amino acid analysis [13].
  • Nevertheless, EKLF binds this atypical site by gel mobility shift assay, specifically occupies the AHSP promoter in vivo in a chromatin immunoprecipitation assay, and transactivates AHSP through this CACC site in promoter-reporter assays [3].
  • The relaxation of the bioassay tissues induced by EDRF was indistinguishable from that induced by NO [19].

References

  1. GATA-1 and Oct-1 are required for expression of the human alpha-hemoglobin-stabilizing protein gene. Gallagher, P.G., Liem, R.I., Wong, E., Weiss, M.J., Bodine, D.M. J. Biol. Chem. (2005) [Pubmed]
  2. Evaluation of alpha hemoglobin stabilizing protein (AHSP) as a genetic modifier in patients with beta thalassemia. Viprakasit, V., Tanphaichitr, V.S., Chinchang, W., Sangkla, P., Weiss, M.J., Higgs, D.R. Blood (2004) [Pubmed]
  3. Genomic organisation and regulation of murine alpha haemoglobin stabilising protein by erythroid Kruppel-like factor. Keys, J.R., Tallack, M.R., Hodge, D.J., Cridland, S.O., David, R., Perkins, A.C. Br. J. Haematol. (2007) [Pubmed]
  4. Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease. Dinh-Xuan, A.T., Higenbottam, T.W., Clelland, C.A., Pepke-Zaba, J., Cremona, G., Butt, A.Y., Large, S.R., Wells, F.C., Wallwork, J. N. Engl. J. Med. (1991) [Pubmed]
  5. EDRF transcripts and diagnosis of variant Creutzfeldt-Jakob disease. Sjögren, M. Lancet (2001) [Pubmed]
  6. Assessing appetite in Dutch elderly with the Appetite, Hunger and Sensory Perception (AHSP) questionnaire. Mathey, M.F. The journal of nutrition, health & aging. (2001) [Pubmed]
  7. An abundant erythroid protein that stabilizes free alpha-haemoglobin. Kihm, A.J., Kong, Y., Hong, W., Russell, J.E., Rouda, S., Adachi, K., Simon, M.C., Blobel, G.A., Weiss, M.J. Nature (2002) [Pubmed]
  8. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Linder, L., Kiowski, W., Bühler, F.R., Lüscher, T.F. Circulation (1990) [Pubmed]
  9. Thiol-containing agents in the management of unstable angina pectoris and acute myocardial infarction. Horowitz, J.D. Am. J. Med. (1991) [Pubmed]
  10. Endothelial dysfunction and atherosclerosis. Vanhoutte, P.M. Eur. Heart J. (1997) [Pubmed]
  11. Endothelium-derived relaxing and contracting factors. Rubanyi, G.M. J. Cell. Biochem. (1991) [Pubmed]
  12. Evidence for inhibition by endothelium-derived relaxing factor of thromboxane A2 receptor-mediated vasoconstriction in the fetal vessels of the human perfused placenta. Gude, N.M., Boura, A.L., King, R.G., Brennecke, S.P., Jamal, O.S., Smith, R., Walters, W.A. Placenta (1992) [Pubmed]
  13. Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin stabilizing protein. Gell, D., Kong, Y., Eaton, S.A., Weiss, M.J., Mackay, J.P. J. Biol. Chem. (2002) [Pubmed]
  14. Impaired binding of AHSP to alpha chain variants: Hb Groene Hart illustrates a mechanism leading to unstable hemoglobins with alpha thalassemic like syndrome. Vasseur-Godbillon, C., Marden, M.C., Giordano, P., Wajcman, H., Baudin-Creuza, V. Blood Cells Mol. Dis. (2006) [Pubmed]
  15. A new pharmacology--drugging stressed folding pathways. Wiseman, R.L., Balch, W.E. Trends in molecular medicine. (2005) [Pubmed]
  16. Transfer of human alpha- to beta-hemoglobin via its chaperone protein: evidence for a new state. Baudin-Creuza, V., Vasseur-Godbillon, C., Pato, C., Préhu, C., Wajcman, H., Marden, M.C. J. Biol. Chem. (2004) [Pubmed]
  17. A research trail over half a century. Furchgott, R.F. Annu. Rev. Pharmacol. Toxicol. (1995) [Pubmed]
  18. The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. Furchgott, R.F. JAMA (1996) [Pubmed]
  19. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Palmer, R.M., Ferrige, A.G., Moncada, S. Nature (1987) [Pubmed]
  20. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. Stamler, J.S., Osborne, J.A., Jaraki, O., Rabbani, L.E., Mullins, M., Singel, D., Loscalzo, J. J. Clin. Invest. (1993) [Pubmed]
  21. Impact of atrial fibrillation duration on postcardioversion recurrence. Schwartzman, D., Musley, S., Koehler, J., Warman, E. Heart rhythm : the official journal of the Heart Rhythm Society. (2005) [Pubmed]
 
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