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Biochem Biophys Res Commun. 2015 May 15;460(4):909-14. doi: 10.1016/j.bbrc.2015.03.115. Epub 2015 Mar 31.

cCMP and cUMP occur in vivo.

Author information

1
Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany; Research Core Unit Metabolomics, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: baehre.heike@mh-hannover.de.
2
Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: hartwig.christina@mh-hannover.de.
3
Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: munder.antje@mh-hannover.de.
4
Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: wolter.sabine@mh-hannover.de.
5
Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: stelzer.tane@mh-hannover.de.
6
Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: Schirmer.bastian@mh-hannover.de.
7
Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: beckert-ulrike81@email.de.
8
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: frankd@mcw.edu.
9
Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: tuemmler.burkhard@mh-hannover.de.
10
Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany; Research Core Unit Metabolomics, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: kaever.volkhard@mh-hannover.de.
11
Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: seifert.roland@mh-hannover.de.

Abstract

Mammalian cells contain the cyclic pyrimidine nucleotides cCMP and cUMP. It is unknown whether these tentative new second messenger molecules occur in vivo. We used high performance liquid chromatography quadrupole tandem mass spectrometry to quantitate nucleoside 3',5'-cyclic monophosphates. cCMP was detected in all organs studied, most notably pancreas, spleen and the female reproductive system. cUMP was not detected in organs, probably due to the intrinsically low sensitivity of mass spectrometry to detect this molecule and organ matrix effects. Intratracheal infection of mice with recombinant Pseudomonas aeruginosa harboring the nucleotidyl cyclase toxin ExoY massively increased cUMP in lung. The identity of cCMP and cUMP in organs was confirmed by high performance liquid chromatography quadrupole time of flight mass spectrometry. cUMP also appeared in serum, urine and faeces following infection. Taken together, this report unequivocally shows for the first time that cCMP and cUMP occur in vivo.

KEYWORDS:

Cyclic pyrimidine nucleotides; ExoY; Mass spectrometry; Pseudomonas aeruginosa

PMID:
25838203
PMCID:
PMC4765920
DOI:
10.1016/j.bbrc.2015.03.115
[Indexed for MEDLINE]
Free PMC Article

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