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01.12.2014 | Research article | Ausgabe 1/2014 Open Access

BMC Gastroenterology 1/2014

Changes of activity and isoforms of alkaline sphingomyelinase (nucleotide pyrophosphatase phosphodiesterase 7) in bile from patients undergoing endoscopic retrograde cholangiopancreatography

Zeitschrift:
BMC Gastroenterology > Ausgabe 1/2014
Autoren:
Rui-Dong Duan, Ulf Hindorf, Yajun Cheng, Per Bergenzaun, Mats Hall, Erik Hertervig, Åke Nilsson
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1471-230X-14-138) contains supplementary material, which is available to authorized users.

Competing interests

No competing interests with others.

Authors’ contributions

RD: conception and design of the experiment, analysis of the samples, data interpretation, manuscript writing. UH: project organization, patient characterization, ERCP performance, data interpretation, manuscript revision. YC: Lab work organization, sample and data analysis. PB and MH: ERCP performance, patient characterization, manuscript revision. EH: project planning, manuscript revision. ÅN: project organization, patient characterization, data interpretation, manuscript writing. All authors read and approved the final manuscript.

Abstract

Background

Alkaline sphingomyelinase (NPP7) is an ecto-enzyme expressed in intestinal mucosa, which hydrolyses sphingomyelin (SM) to ceramide and inactivates platelet activating factor. It is also expressed in human liver and released in the bile. The enzyme may have anti-tumour and anti-inflammatory effects in colon and its levels are decreased in patients with colon cancer and ulcerative colitis. Active NPP7 is translated from a transcript of 1.4 kb, whereas an inactive form from a 1.2 kb mRNA was found in colon and liver cancer cell lines. While the roles of NPP7 in colon cancer have been intensively studied, less is known about the function and implications of NPP7 in the bile. The present study examines the changes of NPP7 in bile of patients with various hepatobiliary diseases.

Methods

Bile samples were obtained at endoscopic retrograde cholangiopancreatography (ERCP) in 59 patients with gallstone, other benign disease, tumour, and primary sclerosing cholangitis (PSC). The NPP7 activity was determined. The appearance of the 1.4 and 1.2 kb products in the bile was examined by Western blot. The results were correlated to the diseases and also plasma bilirubin and alkaline phosphatase.

Results

NPP7 activity in the tumour group was significantly lower than in the gallstone group (p < 0.05). The activity in the tumour plus PSC group was also lower than in gallstone plus other benign disease group (p < 0.05). Within the tumour group NPP7 activity was lowest in cholangiocarcinoma patients, being only 19% of that in gallstone patients. Bilirubin correlated inversely to NPP7 and was higher in the tumour than in the gallstone group. Western blot identified both the 1.4 kb and the 1.2 kb products in most bile samples. The density ratio for the 1.4/1.2 kb products correlated to NPP7 activity significantly. Two patients (one PSC and one cholangiocarcinoma) lacking NPP7 activity had only the 1.2 kb form in bile.

Conclusion

NPP7 activity and the ratio of 1.4/1.2 kb products in bile are significantly decreased in malignancy, particularly in cholangiocarcinoma. The implications of the finding in diagnosis of cholangiocarcinoma and 1.2 kb product in hepatobiliary diseases require further investigation.
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