期刊
ANALYTICAL BIOCHEMISTRY
卷 334, 期 2, 页码 266-275出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ab.2004.08.019
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资金
- NCI NIH HHS [CA77839, CA95103, CA68485, CA90949] Funding Source: Medline
- NCRR NIH HHS [RR00095] Funding Source: Medline
- NHLBI NIH HHS [HL04445] Funding Source: Medline
- NIDDK NIH HHS [DK48831] Funding Source: Medline
- NIGMS NIH HHS [GM15431] Funding Source: Medline
Prostaglandin (PG)E,, is a major cyclooxygenase (COX) product that is important in human physiology and pathophysiology. Quantification of systemic PG production in humans is best assessed by measuring excreted urinary metabolites. Accurate and easy-to-perform assays to quantify the major urinary metabolite of PGE(2), 11alpha-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), do not exist. We now report the development of a robust and facile method to measure urinary PGE-M excretion in humans using stable isotope dilution techniques employing liquid chromatography/tandem mass spectrometry (LC/MS/MS). Concentrations of the metabolite in urine from healthy humans are nearly twofold greater in men than in women (10.4 +/- 1.5 vs. 6.0 +/- 0.7 ng/mg creatinine). Levels of PGE-M in healthy humans are suppressed significantly not only by the nonselective COX inhibitor ibuprofen but also by the COX-2 selective inhibitor rofecoxib, suggesting that the majority of PGE2 formed in vivo is derived from COX-2. Increased COX-2 expression and increased PGE(2) production are associated with malignancy. Levels of PGE-M were found to be greatly increased in humans with unresectable non-small cell cancer of the lung, and this increase is dramatically reduced by administration of the COX-2 inhibitor celecoxib, implying that COX-2 contributes significantly to the overproduction of PGE(2). In summary, quantification of PGE-M using LC/MS/MS provides a facile and accurate method to assess PGE(2) formation in human physiological and pathophysiological processes. (C) 2004 Elsevier Inc. All rights reserved.
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