Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans
Song W-L, Wang M, Ricciotti E, Fries S, Yu Y, Grosser T, Reilly M, Lawson JA, FitzGerald GA (2008)
Journal of Biological Chemistry 283(2): 1179-1188.
Zeitschriftenaufsatz
| Veröffentlicht | Englisch
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Autor*in
Song, Wen-Liang;
Wang, Miao;
Ricciotti, Emanuela;
Fries, Susanne;
Yu, Ying;
Grosser, TiloUniBi
;
Reilly, Muredach;
Lawson, John A.;
FitzGerald, Garret A.
![](https://pub.uni-bielefeld.de/images/icon_orcid.png)
Abstract / Bemerkung
Prostaglandin D2 (PGD2) is a cyclooxygenase (COX) product of arachidonic acid that activates D prostanoid receptors to modulate vascular, platelet, and leukocyte function in vitro. However, little is known about its enzymatic origin or its formation in vivo in cardiovascular or inflammatory disease. 11,15-Dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor PGDM) was identified by mass spectrometry as a metabolite of infused PGD2 that is detectable in mouse and human urine. Using liquid chromatography-tandem mass spectrometry, tetranor PGDM was much more abundant than the PGD2 metabolites, 11β-PGF2α and 2,3-dinor-11β-PGF2α, in human urine and was the only endogenous metabolite detectable in mouse urine. Infusion of PGD2 dose dependently increased urinary tetranor PGDM > 2,3-dinor-11β-PGF2α > 11β-PGF2α in mice. Deletion of either lipocalin-type or hemopoietic PGD synthase enzymes decreased urinary tetranor PGDM. Deletion or knockdown of COX-1, but not deletion of COX-2, decreased urinary tetranor PGDM in mice. Correspondingly, both PGDM and 2,3-dinor-11β-PGF2α were suppressed by inhibition of COX-1 and COX-2, but not by selective inhibition of COX-2 in humans. PGD2 has been implicated in both the development and resolution of inflammation. Administration of bacterial lipopolysaccharide coordinately elevated tetranor PGDM and 2,3-dinor-11β-PGF2α in volunteers, coincident with a pyrexial and systemic inflammatory response, but both metabolites fell during the resolution phase. Niacin increased tetranor PGDM and 2,3-dinor-11β-PGF2α in humans coincident with facial flushing. Tetranor PGDM is an abundant metabolite in urine that reflects modulated biosynthesis of PGD2 in humans and mice.
Erscheinungsjahr
2008
Zeitschriftentitel
Journal of Biological Chemistry
Band
283
Ausgabe
2
Seite(n)
1179-1188
ISSN
00219258
Page URI
https://pub.uni-bielefeld.de/record/2965339
Zitieren
Song W-L, Wang M, Ricciotti E, et al. Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans. Journal of Biological Chemistry. 2008;283(2):1179-1188.
Song, W. - L., Wang, M., Ricciotti, E., Fries, S., Yu, Y., Grosser, T., Reilly, M., et al. (2008). Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans. Journal of Biological Chemistry, 283(2), 1179-1188. https://doi.org/10.1074/jbc.M706839200
Song, Wen-Liang, Wang, Miao, Ricciotti, Emanuela, Fries, Susanne, Yu, Ying, Grosser, Tilo, Reilly, Muredach, Lawson, John A., and FitzGerald, Garret A. 2008. “Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans”. Journal of Biological Chemistry 283 (2): 1179-1188.
Song, W. - L., Wang, M., Ricciotti, E., Fries, S., Yu, Y., Grosser, T., Reilly, M., Lawson, J. A., and FitzGerald, G. A. (2008). Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans. Journal of Biological Chemistry 283, 1179-1188.
Song, W.-L., et al., 2008. Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans. Journal of Biological Chemistry, 283(2), p 1179-1188.
W.-L. Song, et al., “Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans”, Journal of Biological Chemistry, vol. 283, 2008, pp. 1179-1188.
Song, W.-L., Wang, M., Ricciotti, E., Fries, S., Yu, Y., Grosser, T., Reilly, M., Lawson, J.A., FitzGerald, G.A.: Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans. Journal of Biological Chemistry. 283, 1179-1188 (2008).
Song, Wen-Liang, Wang, Miao, Ricciotti, Emanuela, Fries, Susanne, Yu, Ying, Grosser, Tilo, Reilly, Muredach, Lawson, John A., and FitzGerald, Garret A. “Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans”. Journal of Biological Chemistry 283.2 (2008): 1179-1188.
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