REGULATION OF LIVER GROWTH AND FUNCTION

Project: Research project

Description

Disorders of protein metabolism in the liver are central to the
pathogenesis of diabetes and other disease states that affect nutrient
homeostatis. Development of rational approaches to treatment of these
disorders requires knowledge of the basic events involved in the regulation
of hepatic protein metabolism. Therefore, the overall goal of this project
is to provide a better understanding of the mechanisms by which hormones
and nutrients regulate translational and transcriptional events in the
protein synthetic pathway in liver. Studies of translational control are
to focus on peptide-chain initiation using deficiency of single essential
amino acids to induce an inhibition in formation of 40S initiation
complexes, and diabetes to induce an inhibition subsequent to 40S
initiation complex formation. Studies of transcriptional control are to
focus on the mechanism of insulin action on gene transcription. The
specific aims of the studies are: (1) to investigate the mechanism of
inhibition of peptide-chain initiation in livers deprived of single
essential amino acids, particularly the role of eukaroytic initiation
factor eIF-1; (2) to investigate the mechanism of inhibition of
peptide-chain initiation in livers of diabetic animals, particularly the
mount of mRNA and the role of initiation factors involved in mRNA binding;
(3) to further characterize rat liver eIF-2, particularly with respect to
its differences with the reticulocyte-derived factor; (4) to further purify
and characterize the guanine nucleotide exchange factor from rat liver; and
(5) to further define the actions of insulin on the relative abundance of
mRNAs in primary cultures of rat hepatocytes. The studies are to eploy a
number of experimental systems including the perfused liver, suspensions of
isolated hepatocytes, primary cultures of hepatocytes, and a cell-free
protein-synthesizing system derived from isolated hepatocytes. They are
also to utilize a number of methodologies including protein purification,
immunochemical identification and quantitation of proteins, one- and
two-dimensional gel electrophoresis, quantitation of mRNAs by solution and
dot-blot hybridization using specific cDNAs, ligand binding assays, protein
kinase and phosphatase assays, and gene transcription assays. Overall, the
studies desribed in this proposal should help identify mechanisms by which
hormones and nutrients regulate protein synthesis. They should also
provide new insights into biochemical events involved in peptide-chain
initiation and gene expression.
StatusFinished
Effective start/end date5/1/778/31/19

Funding

  • National Institutes of Health: $451,487.00
  • National Institutes of Health: $18,391.00
  • National Institutes of Health
  • National Institutes of Health: $432,352.00
  • National Institutes of Health: $431,842.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $428,272.00
  • National Institutes of Health
  • National Institutes of Health: $334,689.00
  • National Institutes of Health: $408,981.00
  • National Institutes of Health: $403,728.00
  • National Institutes of Health: $411,095.00
  • National Institutes of Health: $213,238.00
  • National Institutes of Health
  • National Institutes of Health: $389,597.00
  • National Institutes of Health: $408,981.00
  • National Institutes of Health: $8,990.00
  • National Institutes of Health
  • National Institutes of Health: $442,980.00
  • National Institutes of Health: $442,685.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $428,328.00
  • National Institutes of Health: $408,981.00
  • National Institutes of Health: $408,981.00
  • National Institutes of Health: $403,728.00
  • National Institutes of Health: $276,117.00
  • National Institutes of Health: $403,729.00
  • National Institutes of Health: $425,805.00
  • National Institutes of Health
  • National Institutes of Health: $444,254.00
  • National Institutes of Health: $412,173.00
  • National Institutes of Health

Fingerprint

Liver
Growth
Food
Proteins
Insulin
Phosphorylation
Hepatocytes
Amino Acids
Gene Expression
Peptide Initiation Factors
Messenger RNA
S 6
Hormones
Peptides
Diet
Protein Biosynthesis
Ribosomes
Fatty Liver
Glucagon
Sirolimus