MODULATION OF TH GENE EXPRESSION BY RESERPINE AND AGE

Project: Research project

Project Details

Description

DESCRIPTION One of the best
examples of adaptation to cardiovascular perturbations at the molecular
level is the induction of tyrosine hydroxylase (TH) in adrenal glands and
sympathetic ganglia in response to reserpine-induced hypotension. It has
been shown that aging is associated with alterations in TH, the rate
limiting enzymatic step in catecholamine (CA) synthesis. However, the role
of TH gene expression in the age-related decline in cardiovascular
homeostatic mechanisms remains to be elucidated. In the research described
in this proposal, the hypothesis will be tested that aging animals are
impaired in the ability to induce TH in response to reserpine because of
alterations in mechanisms regulating TH gene expression. The specific
objectives of this project are the following: 1. The induction of TH
expression in vivo by reserpine will be compared in the adrenal glands of
rats 4-30 months of age: Alterations in the TH protein will be measured
with a specific antibody and correlated with the kinetics of TH activity
and TH mRNA levels. The time course of induction of TH and TH mRNA will be
compared in rats of different ages and correlated with rates of TH mRNA
transcription. Translatability of TH mRNA will be correlated with
alterations in TH protein and activity. Age-related alterations in pre-and
post-synaptic parameters of neurotransmitters that regulate TH induction
will also be correlated with age-related alterations in induction of TH and
TH mRNA. 2. The induction of TH gene expression in vitro will be compared
in cultured adrenal medullas isolated from different aged rats; the
induction of TH and TH mRNA by dexamethasone and nicotinic receptor agonist
will be compared. The time course and magnitude of induction of TH
activity, TH protein levels and TH mRNA will be compared with rates of TH
protein synthesis in situ. TH mRNA transcription will be measured and
compared with time course and magnitude of induction of TH mRNA and TH
activity. 3. The effects of dietary restriction on age-associated
alterations in adrenal TH gene expression will be assessed. In the past
several years, life-long caloric restriction, a treatment that increases
the life-span of mammals, has become a tool to distinguish time-dependent
effects from biological aging. Therefore, dietary restriction will be used
to determine if age-related differences in modulation of TH gene expression
by reserpine in vivo and in culture is integral to the aging process.
StatusFinished
Effective start/end date2/1/916/30/00

Funding

  • National Institutes of Health: $93,536.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $114,993.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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