ALCOHOL EFFECT ON GASTRIC MUCUS TYROSINE SULFATION

Project Details

Description

Although the synthesis of a protein is dictated by its genome, it alone
does not form the complete structure of the protein which is required in
many cases to perform the biological functions. It is the post
translational modifications that play additional role in forming a protein
with optimal biological activity. In gastric mucosa, several
posttranslational modifications responsible for the processing of mucus
glycoproteins and immunoglobulins have been well characterized in
endoplasmic reticulum and in Golgi. But the tyrosine protein sulfation
involving the transfer of sulfate from 3' phosphoadenosine 5'
phosphosulfate to the hydroxyl group of tyrosine in protein has gained
very little attention. Alcohol induced secretion of mucus glycoprotein of
gastric mucosa has been well documented, however, the basic biochemical
events which trigger this process are still unknown. In the present
project, attention is directed to the role of tyrosine sulfation as the
signal for this secretory response. Since our preliminary study indicates
that ethanol stimulates tyrosine sulfation, the proposal mainly concerns
the effect of ethanol on the enzyme responsible for this modification.
Two major secretory proteins will be studied: the N-glycosidic
immunoglobulin which is known to use the tyrosine sulfation as a signal
when its major secretory pathway is impaired and O-glycosidic mucus
glycoproteins. To understand the basic biochemical events involved in the
ethanol stimulation of tyrosylprotein sulfation, gastric mucosa isolated
from rats of control and ethanol fed groups will be used. The differences
in the activity of tyrosylprotein sulfotransferase (TPST) and the
synthesis and secretion of gastric secretory proteins in these two groups
will be investigated. The experiments will include characterization of
the ethanol induced changes in TPST, testing the possible involvement of
other factors and kinetics of the purified enzyme(s). Role of lipids in
ethanol stimulation of TPST and using antibody to TPST the change in TPST
level and its turnover will be investigated. In addition, cDNA encoding
TPST will be isolated and used for evaluation of changes in the TPST m-RNA
levels and its stability in the control and ethanol group. Tyrosylprotein
sulfation dependent secretion of O-glycosidic glycoprotein, N-glycosidic
immunoglobulin and other gastric secretory proteins and their processing
in presence of ethanol will be studied. It is believed that the findings
from this project should improve the understanding on tyrosylprotein
sulfation and its relation to alcoholism.
StatusFinished
Effective start/end date1/1/9512/31/98

Funding

  • National Institute on Alcohol Abuse and Alcoholism
  • National Institute on Alcohol Abuse and Alcoholism
  • National Institute on Alcohol Abuse and Alcoholism

ASJC

  • Biochemistry

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