Abstract

The research project will focus on the structure and regulation of the gene encoding tryptophan hydroxylase (TPH), the rate-limiting enzyme in the synthesis of serotonin. While TPH is known to be regulated through protein kinase-mediated phosphorylation, this key enzyme may also be regulated at the level of gene expression. Using oligonucleotide probes based on cloned, pineal cDNAs encoding TPH, we can detect mRNA from the CNS. We have shown that the CNS mRNA is altered at the 5' end when compared with the cloned, pineal cDNAs. Furthermore, we have shown that pharmacological agents which alter serontonin levels alter steady-state TPH mRNA levels. We now propose to obtain genomic- and CNS-specific cDNA- clones specific for TPH and to study the mechanism of gene regulation. Lastly, we will study the potential involvement of receptor events in the regulation of TPH mRNA levels.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH000855-04
Application #
3070227
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1990-08-01
Project End
1995-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Rutgers University
Department
Type
Schools of Arts and Sciences
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901

  Publications

Liu, C; Hart, R P; Liu, X J et al. (1996) Cloning and characterization of an alternatively processed human type II interleukin-1 receptor mRNA. J Biol Chem 271:20965-72
Carlson, C D; Hart, R P (1996) Activation of acidic sphingomyelinase and protein kinase C zeta is required for IL-1 induction of LIF mRNA in a Schwann cell line. Glia 18:49-58
Carlson, C D; Bai, Y; Ding, M et al. (1996) Interleukin-1 involvement in the induction of leukemia inhibitory factor mRNA expression following axotomy of sympathetic ganglia. J Neuroimmunol 70:181-90
McCormack, R J; Hart, R P; Ganea, D (1996) Expression of NK-1 receptor mRNA in murine T lymphocytes. Neuroimmunomodulation 3:35-46
Carlson, C D; Bai, Y; Jonakait, G M et al. (1996) Interleukin-1 beta increases leukemia inhibitory factor mRNA levels through transient stimulation of transcription rate. Glia 18:141-51
Ericsson, A; Liu, C; Hart, R P et al. (1995) Type 1 interleukin-1 receptor in the rat brain: distribution, regulation, and relationship to sites of IL-1-induced cellular activation. J Comp Neurol 361:681-98
Kuchinke, W; Hart, R P; Jonakait, G M (1995) Identification of mRNAs regulated by interferon-gamma in cultured rat astrocytes by PCR differential display. Neuroimmunomodulation 2:347-55
Liu, C; Bai, Y; Ganea, D et al. (1995) Species-specific activity of rat recombinant interleukin-1 beta. J Interferon Cytokine Res 15:985-92
Ding, M; Hart, R P; Jonakait, G M (1995) Tumor necrosis factor-alpha induces substance P in sympathetic ganglia through sequential induction of interleukin-1 and leukemia inhibitory factor. J Neurobiol 28:445-54
Ding, M; Hart, R P; Shadiack, A M et al. (1994) The interleukin-1-induced increase of substance P in sympathetic ganglia is not mediated by ciliary neurotrophic factor. J Neurosci Res 38:640-7

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