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HPGDS  -  hematopoietic prostaglandin D synthase

Homo sapiens

Synonyms: GST class-sigma, GSTS, GSTS1, GSTS1-1, Glutathione S-transferase, ...
 
 
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Disease relevance of PGDS

  • These data suggest that the suppressive effect of PGDS on the lung injury could be partly mediated by edema formation and inhibition of genes involved in the fibrotic change [1].
  • Both H-PGDS proteins recombinantly expressed in Escherichia coli showed bifunctional activities for PGDS and GST, and had almost the same catalytic properties as the rat enzyme [2].
  • In the present study, we examined whether the PGDS isoforms may help to distinguish stroke and neurodegenerative disease patients from healthy subjects [3].
  • We measured the concentration of lipocalin-type prostaglandin D synthase (PGDS) in cerebrospinal fluid (CSF) and serum in patients 1, 3, 5, 7, 9, 11, 14 and 17 days after subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysms [4].
  • Giving the important roles proposed for the PGDS enzyme and its product, PGD2, the major PG in the mammalian brain, the altered expression of the PGDS gene may contribute to the deleterious effects of hypothyroidism in the central nervous system [5].
 

Psychiatry related information on PGDS

 

High impact information on PGDS

  • To examine the function of prostaglandin (PG) D synthase (PGDS) gene, as well as endogenously produced PGD(2) in sleep regulation in vivo, we generated transgenic (TG) mice that overexpress human PGDS gene to study their sleep behavior [7].
  • In contrast, in arachnoid villi, PGDS was seen in core arachnoid cells rather than in the cap cell cluster or arachnoid cell layer [8].
  • Because human arachnoid and meningioma cells exclusively express PGDS, it can be considered their specific cell marker [8].
  • Glutathione-independent prostaglandin D synthase (PGDS) is an enzyme responsible for biosynthesis of prostaglandin D2 in the CNS and is identical to a major cerebrospinal fluid protein, beta-trace [8].
  • RT-PCR revealed PGDS gene expression in all meningiomas studied, regardless of histological subtypes, and also in human arachnoid villi [8].
 

Chemical compound and disease context of PGDS

 

Biological context of PGDS

 

Anatomical context of PGDS

  • The PGDS complementary DNA (cDNA)-expressing retrovirally transfected fibroblasts were introduced in vivo, and effect of the expression on lung injury induced by bleomycin was investigated in mice [1].
  • The tissue-specific expression of PGDS also varies significantly between human and rat; amongst the tissues examined, variation in expression between the two species was most apparent in spleen and bone marrow [11].
  • Prostaglandin D synthase (PGDS) activity was detected in human seminal plasma (0.05-1.83 nmol/min per milligram protein) [9].
  • Through immunohistochemistry, PGDS was localized in Leydig cells of the testis and in epithelial cells of the prostate and ductus epididymidis [9].
  • Northern blot analysis revealed that mRNA for PGDS was expressed in the testis, prostate, and epididymis [9].
 

Associations of PGDS with chemical compounds

  • PGD synthase (PGDS) catalyzes the isomerization of PGH2 to PGD2 in the presence of sulfhydryl compounds [12].
  • Prostaglandin D2 synthase (PGDS) (beta-trace protein) is a highly abundant cerebrospinal fluid (CSF) glycoprotein [3].
  • When PGD synthase (PGDS), the enzyme that produces PGD2 in the brain, was inhibited by the intracerebroventricular infusion of its selective inhibitors, i.e. tetravalent selenium compounds, the amount of sleep decreased both time and dose dependently [13].
  • Our results suggest that thyroid hormone regulates the expression of the rat lipocalin-type PGDS gene through this element [5].
  • Both glutathione (GSH)-dependent and GSH-independent PGDS isoenzymes exist [14].
 

Regulatory relationships of PGDS

  • In AP-2-deficient HepG2 cells, the H-PGDS promoter activity was enhanced by coexpression with AP-2alpha [15].
 

Other interactions of PGDS

  • Expressions of the FCER1G and PGDS, which are considered to be mast cell-specific genes, were upregulated in the ovarian endometriotic lesions as compared to the normal ovarian tissues [16].
  • We then examined if the levels of PEPC or PGDS correlate with the type of cyst or with other clinicopathological variables [10].
  • OBJECTIVE: To quantify pepsinogen C (PEPC) and prostaglandin D synthase (PGDS) in breast cyst fluid and examine if these two parameters can be used for breast cyst type classification [10].
  • Two genetically distinct PGD(2)-synthesizing enzymes have been identified to date, including hematopoietic- and lipocalin-type PGD synthases (H-PGDS and L-PGDS, respectively) [17].
  • The fold of mPGES-2 is quite similar to those of GSH-dependent hematopoietic prostaglandin D synthase, except for the two large loop sections [18].
 

Analytical, diagnostic and therapeutic context of PGDS

  • Although PGDS activity and the content determined by the immunoassay each highly varied in the seminal plasma, the concentration was significantly (p < 0.001) lower in the oligozoospermic group (2.47 +/- 0.51 microg/ml) than in the normozoospermic group (9.75 +/- 1.49 microg/ml) [9].
  • The pattern of PGDS PTM was analyzed in CSF from patients with various neurological disorders (n = 44) using IEF/immunoblotting techniques [3].
  • MATERIALS AND METHODS: Using immunohistochemistry and Northern and Western blotting, we demonstrate the dynamic regulation of H-type PGD synthase (PGDS) in placenta during gestation; in contrast, L-type PGDS and its PG products were detected in amniotic fluid, with increased amounts associated with labor [19].
  • There was no overlap between seminal plasma PGDS concentration of normal subjects versus vasectomy patients [20].
  • Complementary DNA clones encoding the orthologous human and rat GSH-dependent PGDS (hPGDS and rPGDS, respectively) have been expressed in Escherichia coli, and the recombinant proteins isolated by affinity chromatography [11].

References

  1. Retrovirally introduced prostaglandin D2 synthase suppresses lung injury induced by bleomycin. Ando, M., Murakami, Y., Kojima, F., Endo, H., Kitasato, H., Hashimoto, A., Kobayashi, H., Majima, M., Inoue, M., Kondo, H., Kawai, S., Hayashi, I. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  2. Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase. Conservation of the ancestral genomic structure of sigma-class glutathione S-transferase. Kanaoka, Y., Fujimori, K., Kikuno, R., Sakaguchi, Y., Urade, Y., Hayaishi, O. Eur. J. Biochem. (2000) [Pubmed]
  3. Prostaglandin D2 synthase and its post-translational modifications in neurological disorders. Lescuyer, P., Gandini, A., Burkhard, P.R., Hochstrasser, D.F., Sanchez, J.C. Electrophoresis (2005) [Pubmed]
  4. Acute and transient increase of lipocalin-type prostaglandin D synthase (beta-trace) level in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage. Mase, M., Yamada, K., Iwata, A., Matsumoto, T., Seiki, K., Oda, H., Urade, Y. Neurosci. Lett. (1999) [Pubmed]
  5. Identification of a thyroid hormone response element in the promoter region of the rat lipocalin-type prostaglandin D synthase (beta-trace) gene. García-Fernández, L.F., Urade, Y., Hayaishi, O., Bernal, J., Muñoz, A. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  6. Lipocalin-type prostaglandin D synthase (beta-trace) in cerebrospinal fluid: a useful marker for the diagnosis of normal pressure hydrocephalus. Mase, M., Yamada, K., Shimazu, N., Seiki, K., Oda, H., Nakau, H., Inui, T., Li, W., Eguchi, N., Urade, Y. Neurosci. Res. (2003) [Pubmed]
  7. Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep. Pinzar, E., Kanaoka, Y., Inui, T., Eguchi, N., Urade, Y., Hayaishi, O. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. Prostaglandin D synthase (beta-trace) in human arachnoid and meningioma cells: roles as a cell marker or in cerebrospinal fluid absorption, tumorigenesis, and calcification process. Yamashima, T., Sakuda, K., Tohma, Y., Yamashita, J., Oda, H., Irikura, D., Eguchi, N., Beuckmann, C.T., Kanaoka, Y., Urade, Y., Hayaishi, O. J. Neurosci. (1997) [Pubmed]
  9. Lipocalin-type prostaglandin D synthase in human male reproductive organs and seminal plasma. Tokugawa, Y., Kunishige, I., Kubota, Y., Shimoya, K., Nobunaga, T., Kimura, T., Saji, F., Murata, Y., Eguchi, N., Oda, H., Urade, Y., Hayaishi, O. Biol. Reprod. (1998) [Pubmed]
  10. Quantification of pepsinogen C and prostaglandin D synthase in breast cyst fluid and their potential utility for cyst type classification. Borchert, G.H., Melegos, D.N., Yu, H., Giai, M., Roagna, R., Ponzone, R., Sgro, L., Diamandis, E.P. Clin. Biochem. (1999) [Pubmed]
  11. Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases. Jowsey, I.R., Thomson, A.M., Flanagan, J.U., Murdock, P.R., Moore, G.B., Meyer, D.J., Murphy, G.J., Smith, S.A., Hayes, J.D. Biochem. J. (2001) [Pubmed]
  12. Lipocalin-type and hematopoietic prostaglandin D synthases as a novel example of functional convergence. Urade, Y., Eguchi, N. Prostaglandins Other Lipid Mediat. (2002) [Pubmed]
  13. Molecular mechanisms of sleep-wake regulation: a role of prostaglandin D2. Hayaishi, O. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2000) [Pubmed]
  14. Prostaglandin D2 synthase enzymes and PPARgamma are co-expressed in mouse 3T3-L1 adipocytes and human tissues. Jowsey, I.R., Murdock, P.R., Moore, G.B., Murphy, G.J., Smith, S.A., Hayes, J.D. Prostaglandins Other Lipid Mediat. (2003) [Pubmed]
  15. Transcriptional activation of the human hematopoietic prostaglandin D synthase gene in megakaryoblastic cells. Roles of the oct-1 element in the 5'-flanking region and the AP-2 element in the untranslated exon 1. Fujimori, K., Kanaoka, Y., Sakaguchi, Y., Urade, Y. J. Biol. Chem. (2000) [Pubmed]
  16. Role of immunoreactions and mast cells in pathogenesis of human endometriosis--morphologic study and gene expression analysis. Konno, R., Yamada-Okabe, H., Fujiwara, H., Uchiide, I., Shibahara, H., Ohwada, M., Ihara, T., Sugamata, M., Suzuki, M. Hum. Cell (2003) [Pubmed]
  17. Positioning prostanoids of the D and J series in the immunopathogenic scheme. Herlong, J.L., Scott, T.R. Immunol. Lett. (2006) [Pubmed]
  18. Crystal structure and possible catalytic mechanism of microsomal prostaglandin E synthase type 2 (mPGES-2). Yamada, T., Komoto, J., Watanabe, K., Ohmiya, Y., Takusagawa, F. J. Mol. Biol. (2005) [Pubmed]
  19. Gestational age-dependent up-regulation of prostaglandin D synthase (PGDS) and production of PGDS-derived antiinflammatory prostaglandins in human placenta. Helliwell, R.J., Keelan, J.A., Marvin, K.W., Adams, L., Chang, M.C., Anand, A., Sato, T.A., O'Carroll, S., Chaiworapongsa, T., Romero, R.J., Mitchell, M.D. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  20. Seminal plasma biochemical markers and their association with semen analysis findings. Diamandis, E.P., Arnett, W.P., Foussias, G., Pappas, H., Ghandi, S., Melegos, D.N., Mullen, B., Yu, H., Srigley, J., Jarvi, K. Urology (1999) [Pubmed]
 
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