Award Date

1-1-2005

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Committee Member

Bryan L. Spangelo

Number of Pages

61

Abstract

We investigated the pathway of IL-1beta stimulated IL-6 release and the involvement of different MAPK's effectors. We used three different MAPK inhibitors SB203580 for p38, SP600125 for JNK, and PD98059 for ERK kinases. We described the role of gamma-Aminobutyric acid (GABA) and GABAB receptor in the inhibition of IL-1beta signal transduction; Bioassay results suggest that SB203580 inhibited IL-6 release while the other two MAPK inhibitors had no effect. It also suggested GABA inhibits the IL-1beta stimulated release of IL-6. By Western analysis we found that IL-1beta activated p38 MAPK time dependent fashion and we saw a maximum stimulation occurred at 15 min; To elucidate the IL-1beta signal transduction more clearly we investigated the role of the GABA receptor subclass. We investigated the role of GABA subclass receptors in IL-1beta stimulation of IL-6 from C6 cells. We used muscimol (agonist for GABAA) and Baclofen (agonist for GABAB). Our result suggested that GABAB receptor is involved in IL-1beta stimulation of IL-6 release in C6 cells, while the GABAA receptor agonist muscimol had no effect; We investigated the role of SRIF in the activation of p38 MAPK by IL-1beta and found that it enhanced the activation of p38. From the above results we described the IL-1beta stimulated IL-6 release and the involvement of p38. GABA attenuates the stimulated release of IL-6 and suppressed p38 activation. Thus, GABA and its mimetics may be clinically effective as a treatment for AD. (Abstract shortened by UMI.).

Keywords

Acid; Aminobutyric Cells; Evidence; Gamma; Glioma; Inhibits; Interleukin; Kinase; Map Rat; Release; Role; Stimulated; Vitro

Controlled Subject

Biochemistry; Neurosciences

File Format

pdf

File Size

1648.64 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

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