Prostaglandin D2 synthase explained

Prostaglandin-H2 D-isomerase (PTGDS) is an enzyme that in humans is encoded by the PTGDS gene.^{[1] [2]}

Function

The protein encoded by this gene is a glutathione-independent prostaglandin D synthase that catalyzes the conversion of prostaglandin H₂ (PGH₂) to prostaglandin D₂ (PGD₂). PGD₂ functions as a neuromodulator as well as a trophic factor in the central nervous system. PGD₂ is also involved in smooth muscle contraction/relaxation and is a potent inhibitor of platelet aggregation. This gene is preferentially expressed in brain. Studies with transgenic mice over-expressing this gene suggest that this gene may be also involved in the regulation of non-rapid eye movement sleep.^[2] Furthermore, PTGDS and its product PGD₂ are elevated in the bald-scalp areas of men with male pattern baldness (androgenetic alopecia).^[3]

Clinical use

Prostaglandin D₂ synthase is used clinically as a diagnostic marker for liquorrhea, that is, to check whether fluid leaking from the nose or ear contains cerebrospinal fluid.^[4] This is important in the assessment of head trauma severity. In a medical context, the older term "beta-trace protein" is frequently used to refer to PTGDS.

See also

• Hematopoietic prostaglandin D synthase

Further reading

• White DM, Mikol DD, Espinosa R, Weimer B, Le Beau MM, Stefansson K . Structure and chromosomal localization of the human gene for a brain form of prostaglandin D2 synthase . The Journal of Biological Chemistry . 267 . 32 . 23202–8 . Nov 1992 . 10.1016/S0021-9258(18)50077-6 . 1385416 . free .
• Kuruvilla AP, Hochwald GM, Ghiso J, Castaño EM, Pizzolato M, Frangione B . Isolation and amino terminal sequence of beta-trace, a novel protein from human cerebrospinal fluid . Brain Research . 565 . 2 . 337–40 . Nov 1991 . 1726844 . 10.1016/0006-8993(91)91666-O . 54405256 . free .
• Zahn M, Mäder M, Schmidt B, Bollensen E, Felgenhauer K . Purification and N-terminal sequence of beta-trace, a protein abundant in human cerebrospinal fluid . Neuroscience Letters . 154 . 1–2 . 93–5 . May 1993 . 7689714 . 10.1016/0304-3940(93)90179-O . 42018337 .
• Harrington MG, Aebersold R, Martin BM, Merril CR, Hood L . Identification of a brain-specific human cerebrospinal fluid glycoprotein, beta-trace protein . Applied and Theoretical Electrophoresis . 3 . 5 . 229–34 . 1993 . 7692978 .
• Bastien L, Sawyer N, Grygorczyk R, Metters KM, Adam M . Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype . The Journal of Biological Chemistry . 269 . 16 . 11873–7 . Apr 1994 . 10.1016/S0021-9258(17)32654-6 . 8163486 . free .
• Funk CD, Furci L, FitzGerald GA, Grygorczyk R, Rochette C, Bayne MA, Abramovitz M, Adam M, Metters KM . Cloning and expression of a cDNA for the human prostaglandin E receptor EP1 subtype . The Journal of Biological Chemistry . 268 . 35 . 26767–72 . Dec 1993 . 10.1016/S0021-9258(19)74379-8 . 8253813 . free .
• Abramovitz M, Boie Y, Nguyen T, Rushmore TH, Bayne MA, Metters KM, Slipetz DM, Grygorczyk R . Cloning and expression of a cDNA for the human prostanoid FP receptor . The Journal of Biological Chemistry . 269 . 4 . 2632–6 . Jan 1994 . 10.1016/S0021-9258(17)41991-0 . 8300593 . free .
• Hoffmann A, Conradt HS, Gross G, Nimtz M, Lottspeich F, Wurster U . Purification and chemical characterization of beta-trace protein from human cerebrospinal fluid: its identification as prostaglandin D synthase . Journal of Neurochemistry . 61 . 2 . 451–6 . Aug 1993 . 8336134 . 10.1111/j.1471-4159.1993.tb02145.x . 34300607 .
• Leone MG, Saso L, Del Vecchio A, Mo MY, Silvestrini B, Cheng CY . Micropurification of two human cerebrospinal fluid proteins by high performance electrophoresis chromatography . Journal of Neurochemistry . 61 . 2 . 533–40 . Aug 1993 . 8336140 . 10.1111/j.1471-4159.1993.tb02156.x . 29843974 .
• Giacomelli S, Leone MG, Grima J, Silvestrini B, Cheng CY . Astrocytes synthesize and secrete prostaglandin D synthetase in vitro . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1310 . 3 . 269–76 . Feb 1996 . 8599604 . 10.1016/0167-4889(95)00182-4 . free .
• Blödorn B, Mäder M, Urade Y, Hayaishi O, Felgenhauer K, Brück W . Choroid plexus: the major site of mRNA expression for the beta-trace protein (prostaglandin D synthase) in human brain . Neuroscience Letters . 209 . 2 . 117–20 . May 1996 . 8761996 . 10.1016/0304-3940(96)12614-8 . 34159760 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Yamashima T, Sakuda K, Tohma Y, Yamashita J, Oda H, Irikura D, Eguchi N, Beuckmann CT, Kanaoka Y, Urade Y, Hayaishi O . 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 . The Journal of Neuroscience . 17 . 7 . 2376–82 . Apr 1997 . 9065498 . 10.1523/JNEUROSCI.17-07-02376.1997. 6573504 .
• White DM, Takeda T, DeGroot LJ, Stefansson K, Arnason BG . Beta-trace gene expression is regulated by a core promoter and a distal thyroid hormone response element . The Journal of Biological Chemistry . 272 . 22 . 14387–93 . May 1997 . 9162076 . 10.1074/jbc.272.22.14387 . free .
• Eguchi Y, Eguchi N, Oda H, Seiki K, Kijima Y, Matsu-ura Y, Urade Y, Hayaishi O . Expression of lipocalin-type prostaglandin D synthase (beta-trace) in human heart and its accumulation in the coronary circulation of angina patients . Proceedings of the National Academy of Sciences of the United States of America . 94 . 26 . 14689–94 . Dec 1997 . 9405674 . 25094 . 10.1073/pnas.94.26.14689 . 1997PNAS...9414689E . free .
• Tokugawa Y, Kunishige I, Kubota Y, Shimoya K, Nobunaga T, Kimura T, Saji F, Murata Y, Eguchi N, Oda H, Urade Y, Hayaishi O . Lipocalin-type prostaglandin D synthase in human male reproductive organs and seminal plasma . Biology of Reproduction . 58 . 2 . 600–7 . Feb 1998 . 9475419 . 10.1095/biolreprod58.2.600 . free .
• Saso L, Leone MG, Sorrentino C, Giacomelli S, Silvestrini B, Grima J, Li JC, Samy E, Mruk D, Cheng CY . Quantification of prostaglandin D synthetase in cerebrospinal fluid: a potential marker for brain tumor . Biochemistry and Molecular Biology International . 46 . 4 . 643–56 . Nov 1998 . 9844724 . 10.1080/15216549800204172 . 29770550 . free .
• Blödorn B, Brück W, Tumani H, Michel U, Rieckmann P, Althans N, Mäder M . Expression of the beta-trace protein in human pachymeninx as revealed by in situ hybridization and immunocytochemistry . Journal of Neuroscience Research . 57 . 5 . 730–4 . Sep 1999 . 10462696 . 10.1002/(SICI)1097-4547(19990901)57:5<730::AID-JNR14>3.0.CO;2-7 . 23555031 .
• Pinzar E, Kanaoka Y, Inui T, Eguchi N, Urade Y, Hayaishi O . Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep . Proceedings of the National Academy of Sciences of the United States of America . 97 . 9 . 4903–7 . Apr 2000 . 10781097 . 18330 . 10.1073/pnas.090093997 . 2000PNAS...97.4903P . free .

Notes and References

1. Nagata A, Suzuki Y, Igarashi M, Eguchi N, Toh H, Urade Y, Hayaishi O . Human brain prostaglandin D synthase has been evolutionarily differentiated from lipophilic-ligand carrier proteins . Proceedings of the National Academy of Sciences of the United States of America . 88 . 9 . 4020–4 . May 1991 . 1902577 . 51585 . 10.1073/pnas.88.9.4020 . 1991PNAS...88.4020N . free .
2. Web site: Entrez Gene: PTGDS prostaglandin D2 synthase 21kDa (brain).
3. Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, Loy DE, Zhao T, Blatt HB, Stanton DC, Carrasco L, Ahluwalia G, Fischer SM, FitzGerald GA, Cotsarelis G . Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia . Science Translational Medicine . 4 . 126 . 126ra34 . Mar 2012 . 22440736 . 3319975 . 10.1126/scitranslmed.3003122 .
4. Bachmann G, Petereit H, Djenabi U, Michel O . Predictive values of beta-trace protein (prostaglandin D synthase) by use of laser-nephelometry assay for the identification of cerebrospinal fluid . Neurosurgery . 50 . 3 . 571–6; discussion 576–7 . Mar 2002 . 11841726 . 10.1227/00006123-200203000-00027 .