REGULATION OF LIVER GROWTH AND FUNCTION

Project: Research project

Description

The studies described in this proposal represent a systematic and integrated
investigation of hormonal and nutritional factors involved in the control of
hepatic protein metabolism in the rat, using the whole animal, the perfused
liver and isolated hepatocytes as experimental models. The objectives are 1) to
investigate the effects of diabetes, insulin, glucagon, fasting, protein
depletion and amino acid deprivation on liver protein synthesis; 2) to
distinguish effects of these conditions on the synthesis of secretory proteins,
particularly albumin, from those on retained intracellular proteins; 3) to
identify the biochemical site(s) of action of each hormonal and nutritional
factor; 4) to establish a liver cell-free system in which effects on the partial
reactions of peptide-chain initiation can be studied; 5) to investigate the
utilization of cytoplasmic mRNA, particularly albumin mRNA, by following its
distribution between membrane-bound polysomes, free polysomes and
ribonucleoprotein particles and by determining its poly(A)-chain length,
5'-capping and turnover; and 6) to integrate effects obtained in vitro in an
attempt to explain the alterations in liver protein synthesis which occur in the
whole animal in response to changes in hormonal and nutritional status.
Identification of control sites and regulatory mechanisms will involve the
application of a number of biochemical and molecular biological techniques that
are currently employed in our laboratories, such as identification and
quantitation of intermediary initiation complexes, separation of membrane-bound
and free polysomes, immunochemical quantitation of albumin and
albumin-synthesizing polysomes, quantitation of mRNA by cell-free translation
and cDNA hybridization assays, and size determination of the average poly(A)
length of mRNA.
StatusFinished
Effective start/end date5/1/774/30/86

Funding

  • National Institutes of Health

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Polyribosomes
Liver
Growth
Albumins
Messenger RNA
Proteins
Poly A
Membranes
Cell-Free System
Glucagon
Nutritional Status
Hepatocytes
Fasting
Theoretical Models
Complementary DNA
Insulin
Amino Acids
Peptides