BILIARY EXCRETION OF LYSOSOMAL PROTEIN

Project: Research project

Description

Our overall objective is to define the physiological and biochemical bases for
the release of lysosomal protein into bile. We are exploring the hypothesis
that exocytosis of lysosomal contents into biliary canaliculi is an excretory
route for hepatocyte lysosomes. To date, we have: 1) established valid assay
conditions for 3 lysosomal hydrolases (beta-galactosidase,
N-acetyl-beta-glucosaminidase, and beta-glucoronidase), 2 plasma membrane
enzymes (5'-nucleotidase and alkaline phosphodiesterase 1) and a soluble enzyme
(LDH) in rat bile and liver; 2) demonstrated that coordinate secretion of these
3 lysosomal hydrolases into rat bile occurs to a greater extent than enzymes
known to be associated with mitochondria, endoplasmic reticulum and cell sap; 3)
demonstrated a dissociation of bile flow, biliary lipid output, and biliary
total protein output from biliary lysosomal enzyme secretion under
non-cholestatic and cholestatic conditions; 4) demonstrated in hamsters that a
non-cholestatic dose of ethynylestradiol increases hepatic lysosomal enzyme
activity, an effect blocked by the anti-estrogen, clomiphene; 5) demonstrated
that large molecular weight 3H-Triton WR-1339 purified by molecular sieve
chromatography is both lysosomotropic for hepatocyte lysosomes and excreted into
bile; 6) demonstrated that feeding, but not glucagon and Triton WR-1339,
increases the output of lysosomal protein into bile; 7) successfully overload
the livers of rats with iron and copper which markedly increased the biliary
excretion of these two metals; and 8) initiated a collaborative study in the
guinea pig exploring the role of gastric cell acid hydrolases in the
pathogenesis of gastric ulcers and the relationship of gastric cell lysosomes to
cytoprotection by prostaglandins.
StatusFinished
Effective start/end date12/1/783/31/86

Funding

  • National Institutes of Health

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Bile
Hydrolases
Lysosomes
Hepatocytes
Liver
Phosphodiesterase I
Hexosaminidases
Clomiphene
5'-Nucleotidase
Gastric Acid
Exocytosis
Enzymes
Stomach Ulcer
beta-Galactosidase
Glucagon
Cricetinae
Endoplasmic Reticulum
Prostaglandins
Copper
Stomach

ASJC

  • Medicine(all)