Hepatocystin Is Not Secreted in Cyst Fluid of Hepatocystin Mutant Polycystic Liver Patients
- 18 April 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Proteome Research
- Vol. 7 (6), 2490-2495
- https://doi.org/10.1021/pr8000282
Abstract
Autosomal dominant polycystic liver disease (PCLD) is characterized by multiple liver cysts and is caused by mutations in PRKCSH (hepatocystin). Mechanisms of cystogenesis are unknown, but previous studies have shown that hepatocystin is secreted in vitro. The goal of this study was to determine the fate of hepatocystin in vivo. Using immunoprecipitation, we determined that mutant hepatocystin is secreted from both apical and basolateral cell surface of MDCK cells stably transfected with mutant hepatocystin. Analysis of 60 cyst fluid samples from polycystic livers using Western blot, MALDI-TOF MS or nLC−MS/MS did not detect hepatocystin in liver cyst fluid. We did identify 163 ubiquitous serum proteins. No paracrine or autocrine factors were recognized. Although cyst fluids vary greatly in protein concentration, a PCLD specific protein pattern was not established. In conclusion, hepatocystin is not secreted in PCLD liver cyst fluid, suggesting that mutant hepatocystin is either not produced or degraded intracellularly. PCLD cysts develop from intralobular bile ductules and cyst fluid mainly contains common serum proteins comparable to that of other polycystic diseases.Keywords
This publication has 23 references indexed in Scilit:
- Octreotide Inhibits Hepatic Cystogenesis in a Rodent Model of Polycystic Liver Disease by Reducing Cholangiocyte Adenosine 3′,5′-Cyclic MonophosphateGastroenterology, 2007
- Extensive mutational analysis ofPRKCSH andSEC63 broadens the spectrum of polycystic liver diseaseHuman Mutation, 2006
- Messenger RNA Surveillance: Neutralizing Natural NonsenseCurrent Biology, 2005
- Secretion of cytokines and growth factors into autosomal dominant polycystic kidney disease liver cyst fluidHepatology, 2004
- Mutations in PRKCSH Cause Isolated Autosomal Dominant Polycystic Liver DiseaseAmerican Journal of Human Genetics, 2003
- Quaternary and Domain Structure of Glycoprotein Processing Glucosidase IIBiochemistry, 2001
- Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1The Lancet, 1994
- Rapid identification of proteins by peptide-mass fingerprintingCurrent Biology, 1993
- Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney diseaseHepatology, 1990
- Polycystic Liver Disease: A Study of Cyst Fluid ConstituentsHepatology, 1982