HORMONE-SENSITIVE LIVER ADENYLATE CYCLASES DURING AGING

  • Katz, Michael S (PI)

Project: Research project

Project Details

Description

The activity of hormone-sensitive adenylate cyclases of rat liver is
age-dependent. Catecholamine- and glucagon-stimulated adenylate cyclase
activities increase during post-maturational aging. This proposal has two
specific aims: I. to examine the biochemical alterations, or mechanisms,
underlying the age-related changes of rat liver adenylate cyclase
activities, and II. to define whether these biochemical determinants of
enzyme activity play a physiological role in the regulation of cyclic
AMP-mediated glycogen mobilization during aging. In vitro studies
addressing the first specific aim will examine age-related changes of
individual components of the adenylate cyclase enzyme complex, including
hormone receptors, guanine nucleotide regulatory components, and catalytic
component. Other plasma membrane-bound enzymes (ATPases, 5'-nucleotidase)
as well as plasma membrane lipid composition and fluidity will also be
studied during the post-maturational life span to determine if aging
changes of adenylate cyclases reflect alterations of the plasma membrane.
To address the second specific aim, in vitro studies will examine whether
age-related alterations of catecholamine- and glucagon-sensitive adenylate
cyclases of rat liver are associated with altered control of glycogenolysis
by these agents. Furthermore, since changes of liver adenylate cyclase
activities occurring during early development of the rat do appear to
regulate glycogenolysis, the mechanisms underlying these developmental
changes of enzyme activity will also be investigated to determine if
related molecular events regulate cyclic AMP-mediated glycogenolysis
throughout the life span. The studies of this proposal should provide
important insights into 1) age-related alteration of hormone action at the
plasma membrane and 2) hormonal regulation of physiological changes of
glucose metabolism occurring during aging.
StatusFinished
Effective start/end date3/1/822/28/89

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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