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Gene Review

Hpd  -  4-hydroxyphenylpyruvic acid dioxygenase

Mus musculus

Synonyms: 4-hydroxyphenylpyruvate dioxygenase, 4-hydroxyphenylpyruvic acid oxidase, 4HPPD, F Alloantigen, F protein, ...
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Disease relevance of Hpd


Psychiatry related information on Hpd


High impact information on Hpd


Chemical compound and disease context of Hpd


Biological context of Hpd

  • The double mutant Fah -/- Hpd -/- mice grew normally without evidence of liver and renal disease, showing a phenotype similar to Hpd -/- mice [11].
  • It is suggested that apoptotic death of renal tubular cells, as induced by administration of homogentisate to Fah-/- Hpd-/- mice, was caused by an intrinsic process, and that renal apoptosis and tubular dysfunctions in tubular cells occurred through different pathways [12].
  • The protein has been of interest to immunologists in the areas of self tolerance and the immunogenetics of the anti-F protein response [13].
  • Vascular permeability increased as a function of HPD dose up to 30 mg/kg [14].
  • HPD treatment did not significantly alter production of antibody to sheep red blood cells, as evaluated by hemagglutination or hemolytic assay [9].

Anatomical context of Hpd

  • Sequences of the mouse F protein alleles and identification of a T cell epitope [13].
  • Photodynamic damage to normal tissues, including skin, appears to occur by photooxidative damage to the normal microvasculature as the primary target sensitized by HPD bound to the vascular wall or endothelial cell [14].
  • In contrast, HPD treatment did promote an increased number of spleen colonies in lethally irradiated mice transfused with syngeneic bone marrow [9].
  • Differentiation-dependent expression of catecholamine-stimulated adenylate cyclase. Roles of the beta-receptor and G/F protein in differentiating 3T3-L1 adipocytes [15].
  • The combination of the recombinant vaccinia virus expressing the MSC virus F protein and Vac-MHN resulted in weak syncytium formation [16].

Associations of Hpd with chemical compounds

  • HPD-deficient mice are a good model with which to examine the biological effects of 4-hydroxyphenylpyruvic acid, which is a keto acid that causes no apparent visceral damage [1].
  • In the homogentisate-treated Fah-/- Hpd-/- mice, massive amounts of succinylacetone were excreted into the urine, regardless of treatment with inhibitors [12].
  • Albino, Swiss-Webster mice (female 122-25 g, 5 mice per group) were injected intraperitoneally (IP) with incremental doses of HPD (Photofrin II, Photofrin Medical, Inc.) (1, 10, 20, 30, 40 and 50 mg/kg) [14].
  • No EB leakage occurred in the absence of HPD at any light dose or in the absence of light at any HPC dose [14].
  • Finally, HPD treatment of L1210 leukemic mice did not affect the antitumor activity of cyclophosphamide [9].

Regulatory relationships of Hpd


Other interactions of Hpd

  • Mice vaccinated with rVV expressing the F protein and high levels of IL-2 or IFN-gamma cleared rVV more rapidly than mice inoculated with a control rVV and developed only low levels of RSV-specific serum antibody [17].
  • The intranasal (i.n.) delivery of purified natural F protein (3 microg per vaccine) formulated with CCG-PS resulted in the generation of statistically heightened serum anti-F protein immunoglobulin G (IgG), IgG1, IgG2b, and IgA antibodies [19].
  • The reaction pattern of the MAbs against three strains of RSV identified three additional epitopes on the F protein and no additional epitopes on the G protein [20].

Analytical, diagnostic and therapeutic context of Hpd


  1. Animal models reveal pathophysiologies of tyrosinemias. Endo, F., Tanaka, Y., Tomoeda, K., Tanoue, A., Tsujimoto, G., Nakamura, K. J. Nutr. (2003) [Pubmed]
  2. Hepatocyte injury in tyrosinemia type 1 is induced by fumarylacetoacetate and is inhibited by caspase inhibitors. Kubo, S., Sun, M., Miyahara, M., Umeyama, K., Urakami, K., Yamamoto, T., Jakobs, C., Matsuda, I., Endo, F. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Complete rescue of lethal albino c14CoS mice by null mutation of 4-hydroxyphenylpyruvate dioxygenase and induction of apoptosis of hepatocytes in these mice by in vivo retrieval of the tyrosine catabolic pathway. Endo, F., Kubo, S., Awata, H., Kiwaki, K., Katoh, H., Kanegae, Y., Saito, I., Miyazaki, J., Yamamoto, T., Jakobs, C., Hattori, S., Matsuda, I. J. Biol. Chem. (1997) [Pubmed]
  4. In vivo correction with recombinant adenovirus of 4-hydroxyphenylpyruvic acid dioxygenase deficiencies in strain III mice. Kubo, S., Kiwaki, K., Awata, H., Katoh, H., Kanegae, Y., Saito, I., Yamamoto, T., Miyazaki, J., Matsuda, I., Endo, F. Hum. Gene Ther. (1997) [Pubmed]
  5. Changes in tissue oxygenation and acidity induced by localized microwave hyperthermia and hematoporphyrin phototherapy, an update. Bicher, H.I., Bruley, D.F. Adv. Exp. Med. Biol. (1983) [Pubmed]
  6. Protection against respiratory syncytial virus infection by DNA immunization. Li, X., Sambhara, S., Li, C.X., Ewasyshyn, M., Parrington, M., Caterini, J., James, O., Cates, G., Du, R.P., Klein, M. J. Exp. Med. (1998) [Pubmed]
  7. A binding site for homeodomain and Pax proteins is necessary for L1 cell adhesion molecule gene expression by Pax-6 and bone morphogenetic proteins. Meech, R., Kallunki, P., Edelman, G.M., Jones, F.S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  8. A murine model for type III tyrosinemia: lack of immunologically detectable 4-hydroxyphenylpyruvic acid dioxygenase enzyme protein in a novel mouse strain with hypertyrosinemia. Endo, F., Katoh, H., Yamamoto, S., Matsuda, I. Am. J. Hum. Genet. (1991) [Pubmed]
  9. Hematoporphyrin derivative rescue from toxicity caused by chemotherapy or radiation in a murine leukemia model (L1210). Canti, G., Franco, P., Marelli, O., Ricci, L., Nicolin, A. Cancer Res. (1984) [Pubmed]
  10. Membrane-associated respiratory syncytial virus F protein expressed from a human rhinovirus type 14 vector is immunogenic. Dollenmaier, G., Mosier, S.M., Scholle, F., Sharma, N., McKnight, K.L., Lemon, S.M. Virology (2001) [Pubmed]
  11. Tyrosinaemia type I and apoptosis of hepatocytes and renal tubular cells. Endo, F., Sun, M.S. J. Inherit. Metab. Dis. (2002) [Pubmed]
  12. A mouse model of renal tubular injury of tyrosinemia type 1: development of de Toni Fanconi syndrome and apoptosis of renal tubular cells in Fah/Hpd double mutant mice. Sun, M.S., Hattori, S., Kubo, S., Awata, H., Matsuda, I., Endo, F. J. Am. Soc. Nephrol. (2000) [Pubmed]
  13. Sequences of the mouse F protein alleles and identification of a T cell epitope. Schofield, J.P., Vijayakumar, R.K., Oliveira, D.B. Eur. J. Immunol. (1991) [Pubmed]
  14. Effects of photosensitizer (hematoporphyrin derivative-HPD) and light dose on vascular targets in the albino mouse ear. Davis, R.K., Davis, K., Straight, R.C., Waner, M. Laryngoscope (1988) [Pubmed]
  15. Differentiation-dependent expression of catecholamine-stimulated adenylate cyclase. Roles of the beta-receptor and G/F protein in differentiating 3T3-L1 adipocytes. Lai, E., Rosen, O.M., Rubin, C.S. J. Biol. Chem. (1981) [Pubmed]
  16. Syncytium formation by recombinant vaccinia viruses carrying bovine parainfluenza 3 virus envelope protein genes. Sakai, Y., Shibuta, H. J. Virol. (1989) [Pubmed]
  17. Recombinant vaccinia virus coexpressing the F protein of respiratory syncytial virus (RSV) and interleukin-4 (IL-4) does not inhibit the development of RSV-specific memory cytotoxic T lymphocytes, whereas priming is diminished in the presence of high levels of IL-2 or gamma interferon. Bembridge, G.P., Lopez, J.A., Cook, R., Melero, J.A., Taylor, G. J. Virol. (1998) [Pubmed]
  18. Mutant forms of the F protein of human respiratory syncytial (RS) virus induce a cytotoxic T lymphocyte response but not a neutralizing antibody response and only transient resistance to RS virus infection. Gaddum, R.M., Cook, R.S., Wyld, S.G., López, J.A., Bustos, R., Melero, J.A., Taylor, G. J. Gen. Virol. (1996) [Pubmed]
  19. A novel and effective intranasal immunization strategy for respiratory syncytial virus. Tebbey, P.W., Unczur, C.A., LaPierre, N.A., Hancock, G.E. Viral Immunol. (1999) [Pubmed]
  20. Identification of epitopes on respiratory syncytial virus proteins by competitive binding immunoassay. Anderson, L.J., Hierholzer, J.C., Stone, Y.O., Tsou, C., Fernie, B.F. J. Clin. Microbiol. (1986) [Pubmed]
  21. Transport and binding of hematoporphyrin derivative and related porphyrins by murine leukemia L1210 cells. Kessel, D. Cancer Res. (1981) [Pubmed]
  22. Histidylated lipid-modified Sendai viral envelopes mediate enhanced membrane fusion and potentiate targeted gene delivery. Verma, S.K., Mani, P., Sharma, N.R., Krishnan, A., Kumar, V.V., Reddy, B.S., Chaudhuri, A., Roy, R.P., Sarkar, D.P. J. Biol. Chem. (2005) [Pubmed]
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