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Gene Review

Hp  -  haptoglobin

Rattus norvegicus

Synonyms: Ba1-647, Haptoglobin, Liver regeneration-related protein LRRG173, Zonulin
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Disease relevance of Hp


High impact information on Hp


Chemical compound and disease context of Hp

  • Similarly, CNTFR3alpha specifically antagonizes the induction of gp130 and LIFRbeta tyrosine phosphorylation observed in response to CNTF and wild type soluble CNTFRalpha in the HepG2 hepatoma cell line, as well as the subsequent events leading to haptoglobin synthesis [8].
  • The concentration of free hemoglobin and the binding capacity of haptoglobin in plasma, both indicators of in vivo hemolysis, did not differ between rats fed the salmon oil diet with 100 or 10,000 mg TA/kg [9].
  • Changes associated with tissue injury were assessed by neutropenia, intestinal edema, serum tumor necrosis factor-alpha, serum haptoglobin, plasma aspartate aminotransferase, and histopathology [10].
  • Feeding of ursodeoxycholic and iso-ursodeoxycholic acid markedly down-regulated alpha2-macroglobulin and TIMP-1 expression in cholestasis but did not affect overexpression of beta-fibrinogen and haptoglobin [11].
  • It was found that hepatoma synthesizes fibrinogen, alpha 1-AP-globulin and alpha 1-acid glycoprotein in the amounts comparable to rat liver, whereas formation of albumin and haptoglobin is reduced 5- to 10-fold [12].

Biological context of Hp

  • Previously observed acute phase-dependent elevation of Hp gene transcriptional activity in prenatal liver was accompanied by increased binding affinities of several fetal soluble nucleoproteins and the hormone response element (RE) of the Hp gene (-170/-56) [13].
  • The rat beta-subunit shows a high degree (approximately 80%) of sequence homology with its human counterpart although it possesses only two of the four N-glycosylation sites present in human haptoglobin beta-subunit [14].
  • Nucleotide sequence of rat haptoglobin cDNA. Characterization of the alpha beta-subunit junction region of prohaptoglobin [14].
  • Upregulation of haptoglobin in reactive astrocytes after transient forebrain ischemia in rats [1].
  • p53-like protein binding affinity to the hormone responsive element of the haptoglobin gene in fetal rat livers [13].

Anatomical context of Hp

  • Furthermore, a reverse transcription-polymerase chain reaction study confirmed an elevated Hp mRNA level in the postischemic hippocampus [1].
  • Growth stimulation of hepatic cells in vivo or in vitro suppresses the Hp gene-inducing effects of inflammatory cytokines [15].
  • Using a 351-bp cDNA coding for Hp for northerns and two Hp primers for RT-PCR, we have demonstrated the expression of Hp in Sertoli and Leydig cells, germ cells, and the testis, but not in the epididymis [16].
  • Parenchymal cells, but not Kupffer cells, in the liver were stained with anti-Hb or anti-Hp IgG after administration of Hb in an amount corresponding to the Hb binding capacity of Hp [17].
  • Among these proteins, haptoglobin (Hp) which is related to inhibition of T-cell proliferation was found to be up-regulated following OLT [18].

Associations of Hp with chemical compounds

  • Structure, hormonal regulation, and identification of the interleukin-6- and dexamethasone-responsive element of the rat haptoglobin gene [2].
  • To identify the cis-acting regulatory elements responsive to these hormones, various lengths of 5' Hp gene-flanking regions, including the promoter, were inserted into chloramphenicol acetyltransferase gene expression vectors and transiently introduced into H-35 cells [3].
  • The half-cystine residue at position 15 in the L chain, which participates in the inter-L chain disulfide bridging in human Hp, has been replaced by a leucine residue in canine Hp [19].
  • The plasma protein synthetic capacity and the in vitro response to insulin plus cortisol of perfused livers from insulin-treated diabetic rats were normal for seven of the proteins but moderately decreased for albumin, haptoglobin and C3 [20].
  • Chronic liver damage induced by thioacetamide (TAM) was accompanied by changes in the expression of genes related to growth (beta-actin) and function (albumin and haptoglobin) of the liver [21].

Physical interactions of Hp

  • By DNA binding assays we found the HMG-1 binding sites in the rat Hp gene cis-regulatory subelements A and C and revealed an increase in its DNA-binding after induction of AP response [22].

Regulatory relationships of Hp

  • HMG-1 as regulatory trans-acting protein in the acute phase-induced expression of the rat liver haptoglobin gene [22].

Other interactions of Hp

  • Double immunofluorescence histochemistry confirmed colocalization of the Hp and glial fibrillary acidic protein [1].
  • The results presented in this report offered further evidence for the existence of structural and functional similarities between these two proteins implicating an involvement of HMG-1 in the regulation of the rat Hp gene transcription [22].
  • In this study AO (Albino Oxford) and DA (Dark Augustin) inbred strains of rats, with different resistance to trauma, were used to compare concentrations of Hp, alpha 2-M, IL-1, IL-6 and TNF, before and after tourniquet trauma [23].
  • Furthermore, p42/p44 MAP kinases may function in a TGFbeta-dependent signaling pathway leading to attenuation of haptoglobin expression [24].
  • The IL-1-dependent induction of the acute phase protein gene haptoglobin in IEC-6 cells was decreased in response to the p38 MAP kinase inhibitor SB203580, as determined by Northern blot [25].

Analytical, diagnostic and therapeutic context of Hp


  1. Upregulation of haptoglobin in reactive astrocytes after transient forebrain ischemia in rats. Lee, M.Y., Kim, S.Y., Choi, J.S., Lee, I.H., Choi, Y.S., Jin, J.Y., Park, S.J., Sung, K.W., Chun, M.H., Kim, I.S. J. Cereb. Blood Flow Metab. (2002) [Pubmed]
  2. Structure, hormonal regulation, and identification of the interleukin-6- and dexamethasone-responsive element of the rat haptoglobin gene. Marinković, S., Baumann, H. Mol. Cell. Biol. (1990) [Pubmed]
  3. Distinct regulation of the interleukin-1 and interleukin-6 response elements of the rat haptoglobin gene in rat and human hepatoma cells. Baumann, H., Morella, K.K., Jahreis, G.P., Marinković, S. Mol. Cell. Biol. (1990) [Pubmed]
  4. Effects of pyridoxine on serum protein expression in hepatoma-bearing rats. Tryfiates, G.P. J. Natl. Cancer Inst. (1981) [Pubmed]
  5. Proteolytic cleavage of haptoglobin occurs in a subcompartment of the endoplasmic reticulum: evidence from membrane fusion in vitro. Wassler, M., Fries, E. J. Cell Biol. (1993) [Pubmed]
  6. Differential arrest of secretory protein transport in cultured rat hepatocytes by azide treatment. Persson, R., Ahlström, E., Fries, E. J. Cell Biol. (1988) [Pubmed]
  7. Stimulation of fibrinogen synthesis in cultured rat hepatocytes by fibrinogen degradation product fragment D. LaDuca, F.M., Tinsley, L.A., Dang, C.V., Bell, W.R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  8. Alanine substitution for Thr268 and Asp269 of soluble ciliary neurotrophic factor (CNTF) receptor alpha component defines a specific antagonist for the CNTF response. Auguste, P., Robledo, O., Olivier, C., Froger, J., Praloran, V., Pouplard-Barthelaix, A., Gascan, H. J. Biol. Chem. (1996) [Pubmed]
  9. Excess dietary vitamin E lowers the activities of antioxidative enzymes in erythrocytes of rats fed salmon oil. Eder, K., Flader, D., Hirche, F., Brandsch, C. J. Nutr. (2002) [Pubmed]
  10. Protective effect of a new C5a receptor antagonist against ischemia-reperfusion injury in the rat small intestine. Arumugam, T.V., Shiels, I.A., Woodruff, T.M., Reid, R.C., Fairlie, D.P., Taylor, S.M. J. Surg. Res. (2002) [Pubmed]
  11. Effect of glutathione depletion and hydrophilic bile acids on hepatic acute phase reaction in rats with extrahepatic cholestasis. Roeb, E., Purucker, E., Gartung, C., Geier, A., Jansen, B., Winograd, R., Matern, S. Scand. J. Gastroenterol. (2003) [Pubmed]
  12. Synthesis and secretion of some plasma proteins by tissue slices of Morris hepatoma 7777 and liver from control and turpentine-injected rats. Koj, A., Dubin, A., Kasperczyk, H., Kaczmarski, F., Stankiewicz, D. Folia histochemica et cytochemica. (1983) [Pubmed]
  13. p53-like protein binding affinity to the hormone responsive element of the haptoglobin gene in fetal rat livers. Bogojević, D., Petrović, M., Mihailović, M. Cell Biol. Int. (2002) [Pubmed]
  14. Nucleotide sequence of rat haptoglobin cDNA. Characterization of the alpha beta-subunit junction region of prohaptoglobin. Goldstein, L.A., Heath, E.C. J. Biol. Chem. (1984) [Pubmed]
  15. Haptoglobin, an inflammation-inducible plasma protein. Wang, Y., Kinzie, E., Berger, F.G., Lim, S.K., Baumann, H. Redox Rep. (2001) [Pubmed]
  16. Haptoglobin is a Sertoli cell product in the rat seminiferous epithelium: its purification and regulation. O'Bryan, M.K., Grima, J., Mruk, D., Cheng, C.Y. J. Androl. (1997) [Pubmed]
  17. Immunohistochemical studies on hemoglobin-haptoglobin and hemoglobin catabolism sites. Kino, K., Mizumoto, K., Watanabe, J., Tsunoo, H. J. Histochem. Cytochem. (1987) [Pubmed]
  18. Expression, by functional proteomics, of spontaneous tolerance in rat orthotopic liver transplantation. Pan, T.L., Wang, P.W., Huang, C.C., Goto, S., Chen, C.L. Immunology (2004) [Pubmed]
  19. Amino acid sequence and disulfide-bridge location of canine haptoglobin. Kumazaki, T., Urushibara, N., Ishii, S. J. Biochem. (1992) [Pubmed]
  20. Effects of streptozotocin diabetes in the rat on blood levels of ten specific plasma proteins and on their net biosynthesis by the isolated perfused liver. Miller, L.L., Treat, D.E., Fridd, B., Wemett, D. Hepatology (1990) [Pubmed]
  21. Changes in rat liver gene expression induced by thioacetamide: protective role of S-adenosyl-L-methionine by a glutathione-dependent mechanism. Mesa, M.L., Carrizosa, R., Martínez-Honduvilla, C., Benito, M., Fabregat, I. Hepatology (1996) [Pubmed]
  22. HMG-1 as regulatory trans-acting protein in the acute phase-induced expression of the rat liver haptoglobin gene. Grigorov, I., Milosavljević, T., Cvetković, I., Petrović, M. Gen. Physiol. Biophys. (2001) [Pubmed]
  23. Variability of haptoglobin and alpha 2-macroglobulin in Albino Oxford and Dark Augustin inbred strains of rats before and after trauma. Strnad, M., Radojicić, C., Marinković, D., Magić, Z. Vojnosanitetski pregled. Military-medical and pharmaceutical review. (2000) [Pubmed]
  24. Attenuation of haptoglobin gene expression by TGFbeta requires the MAP kinase pathway. Yu, S.J., Boudreau, F., Désilets, A., Houde, M., Rivard, N., Asselin, C. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  25. IL-1 beta-dependent regulation of C/EBP delta transcriptional activity. Svotelis, A., Doyon, G., Bernatchez, G., Désilets, A., Rivard, N., Asselin, C. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  26. Comparative sequence analysis of the N-terminal region of rat, rabbit, and dog haptoglobin beta-chains. Kurosky, A., Kim, H.H., Touchstone, B. Comp. Biochem. Physiol., B (1976) [Pubmed]
  27. Endometriotic lesions synthesize and secrete a haptoglobin-like protein. Sharpe-Timms, K.L., Piva, M., Ricke, E.A., Surewicz, K., Zhang, Y.L., Zimmer, R.L. Biol. Reprod. (1998) [Pubmed]
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