CHANGES IN PHOSPHOLIPID-DEPENDENT SIGNAL TRANSDUCTION AFTER ALCOHOL EXPOSURE

  • Thomas, Andrew (PI)
  • RUBIN, RAPHAEL (PI)
  • Iswrael, Yedy (PI)
  • Cavarrubias, Maneel (PI)
  • Rubin, Emanuel (PI)
  • Rubin, Emanuel (PI)
  • Hoek, Jan (PI)
  • Taraschi, Theodore (PI)
  • Ellingson, John (PI)
  • THOMAS, ANDREW (PI)
  • Farber, John (PI)
  • Stubbs, Christopher (PI)
  • Baserga, Renato Luigi (PI)
  • Chance, Britton (PI)
  • Rubin, Emanuel (PI)
  • Rubin, Emanuel (PI)
  • HOEK, JOANNES (PI)
  • Taraschi, Theodore (PI)
  • Ellingson, John (PI)
  • Stubbs, Christopher (PI)
  • PONNAPPA (PI)
  • THOMAS, ANDREW (PI)
  • TARASCHI (PI)
  • Farber, John (PI)
  • Baserga, Renato Luigi (PI)
  • Chance, Britton (PI)

Project Details

Description

In recent years, evidence has accumulated that ethanol has significant
effects on phospholipid-dependent signal transduction systems in a
variety of cells and tissues, including liver. The mechanisms of these
actions of ethanol may relate to its ability to interact with the
phospholipid bilayer and to disturb protein-protein interactions or
protein-lipid interactions. As a consequence, ethanol can trigger the
generation of a variety of intracellular signals, dependent on
phospholipase C and other phospholipases and set into motion a train of
events associated with feedback regulation of these signalling systems
by protein kinase C, resulting in a desensitization of some hormonal
responses in the cell. There is evidence that liver cells from
chronically alcoholic rats are tolerant to this heterologous
desensitization, associated with changes in the feedback control by
protein kinase C. Other hormone-sensitive phospholipases may also be
altered in response to chronic ethanol feeding. This study aims a) to
elucidate the changes in the phospholipid dependent signalling processes
and to investigate the role of protein kinase C isozymes in these
changes; b) to analyze the effects of ethanol in vitro on phospholipase-
linked signal transduction systems. In addition, the effects of long-
term exposure to the anesthetic nitrous oxide on the signal transduction
systems in the liver will be compared with those observed after long-term
alcohol consumption. Finally, the effects of prolonged treatment with
ethanol in vitro on the phospholipid-linked signal transduction processes
in a liver-derived cell line, WB cells, will be studied. The results are
expected to increase our understanding of defective responses of the
liver to hormones and growth factors and to help develop a model by which
the mechanism of these adaptive changes can be studied in vitro.
StatusFinished
Effective start/end date1/1/0111/30/03

ASJC

  • Medicine(all)
  • veterinary(all)
  • Cardiology and Cardiovascular Medicine
  • Psychiatry and Mental health
  • Genetics
  • Radiation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Molecular Biology
  • Structural Biology
  • Biochemistry
  • Spectroscopy
  • Cell Biology
  • Filtration and Separation