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Gene Review

Hp  -  haptoglobin

Mus musculus

Synonyms: HP-1, Haptoglobin, Zonulin, preHP2, zonulin
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Disease relevance of Hp


High impact information on Hp

  • Amounts of the serum glycoprotein, haptoglobin, decreased parallel to those of gp70 but amounts of albumin did not [5].
  • Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin [6].
  • Purified hormones produced a significant anabolic response in only a few cases: dexamethasone was found to be effective in maintaining differentiated expression of the cells; and glucagon produced a specific inhibition of haptoglobin synthesis [7].
  • But neither prenatal nor adult hepatocytes showed a dexamethasone-dependent increase in haptoglobin synthesis [8].
  • It appears that haptoglobin expression in mouse liver cells is potentially sensitive to glucocorticoids, but this modulation is manifested only in transformed cells and their derivatives [8].

Chemical compound and disease context of Hp


Biological context of Hp


Anatomical context of Hp

  • Among plasma-protective proteins against oxidative damage caused by red blood cell rupture, haptoglobin and hemopexin are thought to play a crucial role [2].
  • The Hp-/- mouse was generated by a standard gene replacement technique in mouse embryonic stem cells [9].
  • The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme-iron recovery [15].
  • Hepatocytes on matrigel secreted substantially higher amounts of albumin, transferrin, haptoglobin, and hemopexin, Northern blot analyses of extracted cellular RNA, expressed increased amounts of mRNA for the liver-specific protein albumin (as compared with cells on vitrogen) [16].
  • Instead, HP expression in alveolar epithelial cells, most likely type 2 cells, was strongly increased [17].

Associations of Hp with chemical compounds


Regulatory relationships of Hp

  • After intraperitoneal administration of N-CWS to mice, serum hemopexin increased markedly and also induced an increase of haptoglobin, but not of ceruloplasmin [20].
  • On the other hand, Hp expression was induced in mice transgenically expressing TNFalpha in adipose tissue [21].
  • The GT1 strain (inducing 100% mortality at day 9) also gave the fastest response in terms of weight loss (onset by day 8) and increase in serum haptoglobin (onset by day 6), which occurred 1-2 days before these parameters were affected in the other low-dose groups [22].
  • In the liver, haptoglobin expression is mainly regulated by interleukin-6 (IL-6) [23].

Other interactions of Hp


Analytical, diagnostic and therapeutic context of Hp


  1. Extrahepatic expression of plasma protein genes during inflammation. Kalmovarin, N., Friedrichs, W.E., O'Brien, H.V., Linehan, L.A., Bowman, B.H., Yang, F. Inflammation (1991) [Pubmed]
  2. Enhanced splenomegaly and severe liver inflammation in haptoglobin/hemopexin double-null mice after acute hemolysis. Tolosano, E., Fagoonee, S., Hirsch, E., Berger, F.G., Baumann, H., Silengo, L., Altruda, F. Blood (2002) [Pubmed]
  3. Increased susceptibility in Hp knockout mice during acute hemolysis. Lim, S.K., Kim, H., Lim, S.K., bin Ali, A., Lim, Y.K., Wang, Y., Chong, S.M., Costantini, F., Baumman, H. Blood (1998) [Pubmed]
  4. Increased renal hypertrophy in diabetic mice genetically modified at the haptoglobin locus. Miller-Lotan, R., Herskowitz, Y., Kalet-Litman, S., Nakhoul, F., Aronson, D., Zoabi, R., Asaf, R., Ben-Izhak, O., Sabo, E., Lim, S.K., Baumann, H., Berger, F.G., Levy, A.P. Diabetes Metab. Res. Rev. (2005) [Pubmed]
  5. Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice. Izui, S., Fernandes, G., Hara, I., McConahey, P.J., Jensen, F.C., Dixon, F.J., Good, R.A. J. Exp. Med. (1981) [Pubmed]
  6. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. Belcher, J.D., Mahaseth, H., Welch, T.E., Otterbein, L.E., Hebbel, R.P., Vercellotti, G.M. J. Clin. Invest. (2006) [Pubmed]
  7. Synthesis and regulation of acute phase plasma proteins in primary cultures of mouse hepatocytes. Baumann, H., Jahreis, G.P., Gaines, K.C. J. Cell Biol. (1983) [Pubmed]
  8. Regulation of mouse haptoglobin synthesis. Baumann, H., Jahreis, G.P. J. Cell Biol. (1983) [Pubmed]
  9. Consequences of haemolysis without haptoglobin. Lim, S.K. Redox Rep. (2001) [Pubmed]
  10. Haptoglobin dampens endotoxin-induced inflammatory effects both in vitro and in vivo. Arredouani, M.S., Kasran, A., Vanoirbeek, J.A., Berger, F.G., Baumann, H., Ceuppens, J.L. Immunology (2005) [Pubmed]
  11. Haptoglobin reduces renal oxidative DNA and tissue damage during phenylhydrazine-induced hemolysis. Lim, Y.K., Jenner, A., Ali, A.B., Wang, Y., Hsu, S.I., Chong, S.M., Baumman, H., Halliwell, B., Lim, S.K. Kidney Int. (2000) [Pubmed]
  12. Linkage of the gene for uncoupling protein to esterase-1,2 and haptoglobin in the rat. Otsen, M., Den Bieman, M., van Zutphen, L.F. J. Hered. (1993) [Pubmed]
  13. Haptoglobin modifies the hemochromatosis phenotype in mice. Tolosano, E., Fagoonee, S., Garuti, C., Valli, L., Andrews, N.C., Altruda, F., Pietrangelo, A. Blood (2005) [Pubmed]
  14. Characterization of the mouse haptoglobin gene. Yang, F., Linehan, L.A., Friedrichs, W.E., Lalley, P.A., Sakaguchi, A.Y., Bowman, B.H. Genomics (1993) [Pubmed]
  15. Plasma protein haptoglobin modulates renal iron loading. Fagoonee, S., Gburek, J., Hirsch, E., Marro, S., Moestrup, S.K., Laurberg, J.M., Christensen, E.I., Silengo, L., Altruda, F., Tolosano, E. Am. J. Pathol. (2005) [Pubmed]
  16. Regulation of gene expression in adult rat hepatocytes cultured on a basement membrane matrix. Schuetz, E.G., Li, D., Omiecinski, C.J., Muller-Eberhard, U., Kleinman, H.K., Elswick, B., Guzelian, P.S. J. Cell. Physiol. (1988) [Pubmed]
  17. Cell type-specific and inflammatory-induced expression of haptoglobin gene in lung. Yang, F., Friedrichs, W.E., Navarijo-Ashbaugh, A.L., deGraffenried, L.A., Bowman, B.H., Coalson, J.J. Lab. Invest. (1995) [Pubmed]
  18. Regulation of haptoglobin gene expression in 3T3-L1 adipocytes by cytokines, catecholamines, and PPARgamma. do Nascimento, C.O., Hunter, L., Trayhurn, P. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  19. Macrophage-mediated acute-phase transport protein production induced by lentinan. Suga, T., Maeda, Y.Y., Uchida, H., Rokutanda, M., Chihara, G. Int. J. Immunopharmacol. (1986) [Pubmed]
  20. Effect of Nocardia rubra cell wall skeleton on humoral and cellular factors related to immune response in mice and guinea pigs. Mine, Y., Watanabe, Y., Tawara, S., Yokota, Y., Kikuchi, H. Arzneimittel-Forschung. (1986) [Pubmed]
  21. Obesity modulates the expression of haptoglobin in the white adipose tissue via TNFalpha. Chiellini, C., Bertacca, A., Novelli, S.E., Görgün, C.Z., Ciccarone, A., Giordano, A., Xu, H., Soukas, A., Costa, M., Gandini, D., Dimitri, R., Bottone, P., Cecchetti, P., Pardini, E., Perego, L., Navalesi, R., Folli, F., Benzi, L., Cinti, S., Friedman, J.M., Hotamisligil, G.S., Maffei, M. J. Cell. Physiol. (2002) [Pubmed]
  22. A study of virulence parameters for Toxoplasma gondii infections in mice. Jensen, L., Heegaard, P.M., Lind, P. Parasitol. Res. (1998) [Pubmed]
  23. Nitric oxide synthesis is involved in arterial haptoglobin expression after sustained flow changes. Smeets, M.B., Pasterkamp, G., Lim, S.K., Velema, E., van Middelaar, B., de Kleijn, D.P. FEBS Lett. (2002) [Pubmed]
  24. Interleukin-1 and interleukin-6 stimulate acute-phase protein production in primary mouse hepatocytes. Prowse, K.R., Baumann, H. J. Leukoc. Biol. (1989) [Pubmed]
  25. Ultraviolet-induced cyclobutane pyrimidine dimers are selectively removed from transcriptionally active genes in the epidermis of the hairless mouse. Ruven, H.J., Berg, R.J., Seelen, C.M., Dekkers, J.A., Lohman, P.H., Mullenders, L.H., van Zeeland, A.A. Cancer Res. (1993) [Pubmed]
  26. Gene expression of lipid binding protein transferred the ability of specific attachment of hemopoietic cells to non-supportive stromal cell line, MS-K. Takashita, E., Sugimoto, K., Jiang, H., Tohma, M., Urano, E., Yokoyama, H., Mori, K.J. Cell Struct. Funct. (1997) [Pubmed]
  27. Retinal capillary basement membrane thickness in diabetic mice genetically modified at the haptoglobin locus. Miller-Lotan, R., Miller, B., Nakhoul, F., Aronson, D., Asaf, R., Levy, A.P. Diabetes Metab. Res. Rev. (2007) [Pubmed]
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