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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA005858-08
Application #
3109139
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1988-06-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
605799469
City
Newark
State
NJ
Country
United States
Zip Code
07107
Slomiany, A; Nowak, P; Piotrowski, E et al. (1998) Effect of ethanol on intracellular vesicular transport from Golgi to the apical cell membrane: role of phosphatidylinositol 3-kinase and phospholipase A2 in Golgi transport vesicles association and fusion with the apical membrane. Alcohol Clin Exp Res 22:167-75
Slomiany, A; Morita, M; Sano, S et al. (1997) Effect of ethanol on gastric mucus glycoprotein synthesis, translocation, transport, glycosylation, and secretion. Alcohol Clin Exp Res 21:417-23
Piotrowski, J; Majka, J; Slomiany, A et al. (1995) Helicobacter pylori lipopolysaccharide inhibition of gastric mucosal somatostatin receptor. Biochem Mol Biol Int 36:491-8
Slomiany, A; Grabska, M; Piotrowski, E et al. (1994) Intracellular processes associated with vesicular transport from endoplasmic reticulum to Golgi and exocytosis: ethanol-induced changes in membrane biogenesis. Arch Biochem Biophys 310:247-55
Kasinathan, C; Sundaram, P; Slomiany, B L et al. (1993) Inhibition of tyrosylprotein sulfotransferase by sphingosine and its reversal by acidic phospholipids. Biochemistry 32:1194-8
Slomiany, A; Grabska, M; Slomiany, B A et al. (1993) Intracellular transport, organelle biogenesis and establishment of Golgi identity: impact of brefeldin A on the activity of lipid synthesizing enzymes. Int J Biochem 25:891-901
Slomiany, B L; Piotrowski, J; Czajkowski, A et al. (1993) Characterization of gastric mucosal mucin receptor. Biochem Mol Biol Int 31:745-53
Zirvi, K A; Najjar, T A; Slomiany, B L (1993) Sensitivity of human colon tumor metastases to anticancer drugs in athymic (nude) mice. Cancer Lett 72:39-44
Zirvi, K A; Keogh, J P; Slomiany, A et al. (1993) Effects of exogenous transglutaminase on spreading of human colorectal carcinoma cells. Cancer Biochem Biophys 13:283-94
Keogh, J P; Zirvi, K A; Vossough, S et al. (1993) Pharmacological alterations of cellular transglutaminase activity and invasiveness in human colorectal carcinoma cells. Cancer Biochem Biophys 13:209-20

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