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Gene Review

PTGDS  -  prostaglandin D2 synthase 21kDa (brain)

Homo sapiens

Synonyms: Beta-trace protein, Cerebrin-28, Glutathione-independent PGD synthase, L-PGDS, LPGDS, ...
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Disease relevance of PTGDS

  • PTGDS protein is a seminal plasma biomarker for differentiation between obstructive (OA) and non-obstructive (NOA) azoospermia [1], [2].
  • However, the veno-arterial difference in the plasma L-PGDS concentration was not observed in normal subjects without stenosis [3].
  • The urinary excretion was correlated independently with urinary protein excretion even when there was no difference in urinary protein or albumin excretions, thereby suggesting that urinary L-PGDS excretion is possibly a more sensitive indicator of renal injuries than proteinuria [4].
  • RESULTS: Plasma L-PGDS concentration was slightly higher in the patients with diabetes mellitus than in the control subjects, whereas the urinary L-PGDS excretion almost doubled in the diabetic patients as compared with that in the control subjects [4].
  • CONCLUSIONS: Urinary L-PGDS excretion increased in the early stage of kidney injury in patients with type-2 diabetes mellitus [4].
  • However, little is known about the implications of L-PGDS in hypertension [5].

Psychiatry related information on PTGDS

  • CONCLUSIONS: The circadian L-PGDS pattern and its suppression by total sleep deprivation indicate an interaction of the prostaglandin D system and human sleep regulation [6].
  • It appears that SD causes increases in prostaglandin D2 (PGD2) and 2-arachidonylglycerol (2-AG), and a decrease in PGE2, suggesting that these lipid messengers participate in memory consolidation during REM sleep [7].
  • Thus, growth suppression of PPARgamma-expressing tumor cells by PGD2 metabolites in the prostate microenvironment is likely to be an endogenous mechanism involved in tumor suppression that potentially contributes to the indolence and long latency period of this disease [8].
  • Contribution of prostaglandin D2 synthase to progression of renal failure and dialysis dementia [9].
  • The Proxy for the Deficit Syndrome (PDS; Kirkpatrick, B., Buchanan, R.W., Carpenter, W.T., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Research 47, 47-56.) was calculated based on psychiatric symptoms rated on the Brief Psychiatric Rating Scale every 2 weeks throughout the 12 months [10].

High impact information on PTGDS

  • Activated mast cells release various chemical mediators, including prostaglandin D2 (PGD2), whose role in allergic asthma has now been investigated by the generation of mice deficient in the PGD receptor (DP) [11].
  • CRTH2+CD4+ TH2 memory cells activated by TSLP-DCs undergo further TH2 polarization and express cystatin A, Charcot-Leydon crystal protein, and prostaglandin D2 synthase, implying their broader roles in allergic inflammation [12].
  • Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions [13].
  • PGD2 and PGE2 accumulated in the culture medium at the stages of trophozoites and schizonts more actively than at the ring stage [14].
  • In contrast, the time course of prostaglandin D2 (PGD2) or 9 alpha, 11 beta PGF2 (11 beta PGF2) formation did not correlate with lyso-PL generation [15].

Chemical compound and disease context of PTGDS


Biological context of PTGDS


Anatomical context of PTGDS


Associations of PTGDS with chemical compounds


Regulatory relationships of PTGDS


Other interactions of PTGDS

  • Prostaglandin E2 (PGE2) pathway was significantly prevalent in symptomatic plaques, whereas PGD2 pathway was overexpressed in asymptomatic ones, associated with NF-kappaB inactivation and MMP-9 suppression [22].
  • Upon stimulation with anti-CD3 plus anti-CD28 mAbs, coordinated cyclooxygenase-2 expression and PGD2 production were induced in Th2 lines. hPGDS expression was also observed in a small population (<1.0%) of peripheral blood CD4+ lymphocytes from healthy adults [26].
  • Only Ca Ion stimulated prostaglandin D2 (PGD2) production while IL-1 beta, and Ca Ion, but not LPS, increased prostaglandin F2 alpha (PGF2 alpha) formation [27].
  • As the PGD2 metabolite, 15-deoxy-Delta12,14-PGJ2, can act as a negative regulator of inflammation, these TSG-6 actions may explain, at least in part, the anti-inflammatory effect of TSG-6 observed in the intact organism [28].
  • Cyclooxygenase inhibitors affected the PGD2 release from the cell by IgE-anti IgE challenge incubation [29].

Analytical, diagnostic and therapeutic context of PTGDS


  1. Differential Diagnosis of Azoospermia with Proteomic Biomarkers ECM1 and TEX101 Quantified in Seminal Plasma. Drabovich, A.P., Dimitromanolakis, A., Saraon, P., Soosaipillai, A., Batruch, I., Mullen, B., Jarvi, K., Diamandis, E.P. Sci. Transl. Med. (2013) [Pubmed]
  2. Verification of male infertility biomarkers in seminal plasma by multiplex selected reaction monitoring assay. Drabovich, A.P., Jarvi, K., Diamandis, E.P. Mol. Cell. Proteomics. (2011) [Pubmed]
  3. Expression of lipocalin-type prostaglandin D synthase (beta-trace) in human heart and its accumulation in the coronary circulation of angina patients. Eguchi, Y., Eguchi, N., Oda, H., Seiki, K., Kijima, Y., Matsu-ura, Y., Urade, Y., Hayaishi, O. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  4. Urinary prostaglandin D synthase (beta-trace) excretion increases in the early stage of diabetes mellitus. Hirawa, N., Uehara, Y., Ikeda, T., Gomi, T., Hamano, K., Totsuka, Y., Yamakado, M., Takagi, M., Eguchi, N., Oda, H., Seiki, K., Nakajima, H., Urade, Y. Nephron (2001) [Pubmed]
  5. Lipocalin-type prostaglandin d synthase in essential hypertension. Hirawa, N., Uehara, Y., Yamakado, M., Toya, Y., Gomi, T., Ikeda, T., Eguchi, Y., Takagi, M., Oda, H., Seiki, K., Urade, Y., Umemura, S. Hypertension (2002) [Pubmed]
  6. Prostaglandin D synthase (beta-trace) in healthy human sleep. Jordan, W., Tumani, H., Cohrs, S., Eggert, S., Rodenbeck, A., Brunner, E., Rüther, E., Hajak, G. Sleep. (2004) [Pubmed]
  7. Lipid signaling: sleep, synaptic plasticity, and neuroprotection. Chen, C., Bazan, N.G. Prostaglandins Other Lipid Mediat. (2005) [Pubmed]
  8. Suppression of prostate tumor cell growth by stromal cell prostaglandin D synthase-derived products. Kim, J., Yang, P., Suraokar, M., Sabichi, A.L., Llansa, N.D., Mendoza, G., Subbarayan, V., Logothetis, C.J., Newman, R.A., Lippman, S.M., Menter, D.G. Cancer Res. (2005) [Pubmed]
  9. Contribution of prostaglandin D2 synthase to progression of renal failure and dialysis dementia. Maesaka, J.K., Palaia, T., Fishbane, S., Ragolia, L. Semin. Nephrol. (2002) [Pubmed]
  10. MMPI discriminators of deficit vs. non-deficit recent-onset schizophrenia patients. Subotnik, K.L., Nuechterlein, K.H., Ventura, J. Psychiatry research. (2000) [Pubmed]
  11. Prostaglandin D2 as a mediator of allergic asthma. Matsuoka, T., Hirata, M., Tanaka, H., Takahashi, Y., Murata, T., Kabashima, K., Sugimoto, Y., Kobayashi, T., Ushikubi, F., Aze, Y., Eguchi, N., Urade, Y., Yoshida, N., Kimura, K., Mizoguchi, A., Honda, Y., Nagai, H., Narumiya, S. Science (2000) [Pubmed]
  12. Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Wang, Y.H., Ito, T., Wang, Y.H., Homey, B., Watanabe, N., Martin, R., Barnes, C.J., McIntyre, B.W., Gilliet, M., Kumar, R., Yao, Z., Liu, Y.J. Immunity (2006) [Pubmed]
  13. Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions. Mandal, A.K., Zhang, Z., Ray, R., Choi, M.S., Chowdhury, B., Pattabiraman, N., Mukherjee, A.B. J. Exp. Med. (2004) [Pubmed]
  14. Plasmodium falciparum produces prostaglandins that are pyrogenic, somnogenic, and immunosuppressive substances in humans. Kilunga Kubata, B., Eguchi, N., Urade, Y., Yamashita, K., Mitamura, T., Tai, K., Hayaishi, O., Horii, T. J. Exp. Med. (1998) [Pubmed]
  15. Antigen-induced generation of lyso-phospholipids in human airways. Chilton, F.H., Averill, F.J., Hubbard, W.C., Fonteh, A.N., Triggiani, M., Liu, M.C. J. Exp. Med. (1996) [Pubmed]
  16. The PPARgamma ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines. Morosetti, R., Servidei, T., Mirabella, M., Rutella, S., Mangiola, A., Maira, G., Mastrangelo, R., Koeffler, H.P. Int. J. Oncol. (2004) [Pubmed]
  17. Prostaglandin E2, a seminal constituent, facilitates the replication of acquired immune deficiency syndrome virus in vitro. Kuno, S., Ueno, R., Hayaishi, O., Nakashima, H., Harada, S., Yamamoto, N. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  18. Thromboxane A2, prostacyclin and aspirin: effects on vascular tone and platelet aggregation. Smith, J.B., Araki, H., Lefer, A.M. Circulation (1980) [Pubmed]
  19. Activator protein-1 mediates shear stress-induced prostaglandin d synthase gene expression in vascular endothelial cells. Miyagi, M., Miwa, Y., Takahashi-Yanaga, F., Morimoto, S., Sasaguri, T. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  20. Micropurification of two human cerebrospinal fluid proteins by high performance electrophoresis chromatography. Leone, M.G., Saso, L., Del Vecchio, A., Mo, M.Y., Silvestrini, B., Cheng, C.Y. J. Neurochem. (1993) [Pubmed]
  21. 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]
  22. Balance between PGD synthase and PGE synthase is a major determinant of atherosclerotic plaque instability in humans. Cipollone, F., Fazia, M., Iezzi, A., Ciabattoni, G., Pini, B., Cuccurullo, C., Ucchino, S., Spigonardo, F., De Luca, M., Prontera, C., Chiarelli, F., Cuccurullo, F., Mezzetti, A. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  23. Effect of cyclooxygenase inhibition on cholesterol efflux proteins and atheromatous foam cell transformation in THP-1 human macrophages: a possible mechanism for increased cardiovascular risk. Chan, E.S., Zhang, H., Fernandez, P., Edelman, S.D., Pillinger, M.H., Ragolia, L., Palaia, T., Carsons, S., Reiss, A.B. Arthritis Res. Ther. (2007) [Pubmed]
  24. Beta-trace gene expression is regulated by a core promoter and a distal thyroid hormone response element. White, D.M., Takeda, T., DeGroot, L.J., Stefansson, K., Arnason, B.G. J. Biol. Chem. (1997) [Pubmed]
  25. Human group IIA secretory phospholipase A2 induces neuronal cell death via apoptosis. Yagami, T., Ueda, K., Asakura, K., Hata, S., Kuroda, T., Sakaeda, T., Takasu, N., Tanaka, K., Gemba, T., Hori, Y. Mol. Pharmacol. (2002) [Pubmed]
  26. Cutting edge: differential production of prostaglandin D2 by human helper T cell subsets. Tanaka, K., Ogawa, K., Sugamura, K., Nakamura, M., Takano, S., Nagata, K. J. Immunol. (2000) [Pubmed]
  27. Contribution of cyclooxygenase-1 and cyclooxygenase-2 to prostanoid formation by human enterocytes stimulated by calcium ionophore and inflammatory agents. Longo, W.E., Panesar, N., Mazuski, J., Kaminski, D.L. Prostaglandins Other Lipid Mediat. (1998) [Pubmed]
  28. Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line. Mindrescu, C., Le, J., Wisniewski, H.G., Vilcek, J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  29. IgE-anti-IgE-induced prostaglandin D2 release from cultured human mast cells. Obata, T., Nagakura, T., Kanbe, M., Masaki, T., Maekawa, K., Yamashita, K. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  30. Charge microheterogeneity of the beta-trace proteins (lipocalin-type prostaglandin D synthase) in the cerebrospinal fluid of patients with neurological disorders analyzed by capillary isoelectrofocusing. Hiraoka, A., Seiki, K., Oda, H., Eguchi, N., Urade, Y., Tominaga, I., Baba, K. Electrophoresis (2001) [Pubmed]
  31. Purification and N-terminal sequence of beta-trace, a protein abundant in human cerebrospinal fluid. Zahn, M., Mäder, M., Schmidt, B., Bollensen, E., Felgenhauer, K. Neurosci. Lett. (1993) [Pubmed]
  32. Prostaglandin D synthase isoforms from cerebrospinal fluid vary with brain pathology. Harrington, M.G., Fonteh, A.N., Biringer, R.G., R Hühmer, A.F., Cowan, R.P. Dis. Markers (2006) [Pubmed]
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