Proteins bound for the cell surface, lysosomes and secretory storage granules share a common pathway of intracellular transport. After their synthesis and translocation into the endoplasmic reticulum, these proteins traverse the secretory pathway by a series of vesicular transfers. Little is known about the mechanisms by which proteins are translocated, transported with ER, collected into transport vesicles, or how these vesicles form, identify their targets and subsequently fuse with their target membrane. While under normal conditions, an extensive flow of proteins and lipids is sustained, in presence of ethanol the transport is arrested and mucin precursors accumulate in endoplasmic reticulum. To understand the biochemical mechanisms fundamental to exocytosis and to ethanol-induced impairments in the transport, a number of processes required to take place in ordered sequence to facilitate the flow will be evaluated. Effect of ethanol on mucin translocation, early processing, vesicles formation, budding and mucin delivery to Gogi cisternae will be investigated. Vectorial transport of mucin from ER to Golgi will be evaluated in semi-intact cells with preserved organelle integrity and an option to manipulate their cytoplasmic content. Experiments will be conducted to evaluate if ethanol can arrest generation of transport vesicles and whether the transient vesicular coat reflects intermittent association of cytidyltransferase with those membranes. It is hoped that these studies will provide information on the role of glycoprotein processing and lipids synthesis in exocytic pathway and be of value in attempts to ameliorate some of the gastrointestinal consequences associated with alcohol abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA005858-10
Application #
3109135
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1988-06-01
Project End
1996-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
10
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Dentistry
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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