EFFECT OF ALCOHOL ON GASTRIC MUCUS GLYCOCONJUGATES

Project Details

Description

This research proposal is aimed toward elucidation of chronic effects of
ethanol on gastric mucus structure and function, and on metabolic activity
of gastric mucosa. Since a definite evidence was obtained that ethanol
depletes gastric epithelium of its extracellular mucus and intracellular
stores of mucus glycoprotein, and produces gastric mucosal injury resulting
in the erosions, superficial ulcers, bleeding and chronic gastritis, these
studies are aimed toward elucidation of chronic and acute effects of
ethanol on various stages of mucus glycoprotein synthesis, modification,
elongation of the oligosaccharide chains, secretion, and intracellular
storage. The effect of ethanol on mucus glycoprotein synthesis will be
evaluated with consideration of the intracellular ratio of NAD+/NADH and
endogenous level of prostaglandins, since the change in the redox status is
detrimental to the intermediary metabolism, while prostaglandins are
involved in the cellular protection. The synthesis and its stages i.e.
apoprotein synthesis, acylation, initial glycosylation, elongation,
intracellular storage, and secretion will be studied on gastric mucosa cell
suspension subjected to short term tissue culture in presence of
radiolabeled (3H)proline, (3H)palmitic acid, and
(14C)N-acetylgalactosamine. These experiments will show the timetable of
0-fatty acyl incorporation and 0-glycosylation, and will allow to determine
the effect of ethanol on the rate of glycoprotein synthesis, secretion, and
the intracellular content of glycoprotein and its acylated and glycosylated
precursors. The measurement of the rate of incorporation of the
(14C)carbohydrate from their respective sugar nucleotides to known
glycopeptide acceptors and isolation of the labeled and reduced
oligosaccharides will permit to determine whether ethanol affects the rate
of glycosylation, the path of glycosylation, and the pool of synthesized
apoprotein capable to enter the process of glycosylation with
N-acetylgalactosamine. The in vivo studies will allow to follow the
effects of ethanol on the metabolic activity of gastric mucosa, and these
in vitro to evaluate the effect of ethanol on a one variable at the time.
The proposed studies should provide the conclusive evidence with regard to
the fundamental understanding of the processes involved in the mucus
glycoprotein assembly, their modification in presence of ethanol, as well
as it will add to our understanding of the protective role of
prostaglandins in gastric mucosa.
StatusFinished
Effective start/end date4/1/833/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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