IDENTIFICATION OF B10, AN ALKALINE PHOSPHODIESTERASE OF THE APICAL PLASMA-MEMBRANE OF HEPATOCYTES AND BILIARY CELLS, IN RAT SERUM - INCREASED LEVELS FOLLOWING BILE-DUCT LIGATION AND DURING THE DEVELOPMENT OF CHOLANGIOCARCINOMA
Nr. Meerson et al., IDENTIFICATION OF B10, AN ALKALINE PHOSPHODIESTERASE OF THE APICAL PLASMA-MEMBRANE OF HEPATOCYTES AND BILIARY CELLS, IN RAT SERUM - INCREASED LEVELS FOLLOWING BILE-DUCT LIGATION AND DURING THE DEVELOPMENT OF CHOLANGIOCARCINOMA, Hepatology, 27(2), 1998, pp. 563-568
Alkaline phosphodiesterase (APDE) is associated with the cellular plas
ma membrane of many organs. Several isoforms are also detected in norm
al human serum and their respective amounts vary in liver diseases but
their significance is unknown. The aims of this study were: 1) to ide
ntify a serum form of B10, an APDE exclusively localized at the apical
pole of the plasma membrane of rat hepatocytes and biliary cells; 2)
to gain insight into its origin; and 3) to investigate its behavior, i
n two liver diseases in which an abnormal membrane expression of B10 h
as been reported, namely cholestasis and cholangiocarcinoma. A soluble
form of B10 was immunoprecipitated from normal rat serum, which amoun
ted to 13% of total serum APDE activity. By sodium dodecyl sulfate-pol
yacrylamide gel electrophoresis, the size of the serum enzyme was 125
kd, which is slightly lower than that found in the plasma membrane (13
0 kd). In bile, a 120-kd and a 130-kd form was found. A sixfold and fi
vefold increase of B10 APDE activity was observed in the serum of bile
duct-ligated rats and in the Long-Evans Cinnamon (LEC) rats which spo
ntaneously develop cholangiocarcinoma. The molecular size of the form
present in serum was unchanged. A threefold increase was also observed
in LEC rats which had not yet developed a cholangiocarcinoma. In conc
lusion, we identified a soluble form of B10 in normal rat serum. The i
ncrease in serum B10 in the experimental and pathological conditions i
nvestigated does not seem to result from passage of the biliary form t
o the serum but seems to be caused by increased cleavage of the membra
ne form. Its rise early during the onset of cholangiocarcinoma suggest
s that B10 in the serum might be a marker of carcinogenesis and/or be
involved in the development of cholangiocarcinoma.