Regulation of SULT2B1a (pregnenolone sulfotransferase) expression in rat C6 glioma cells: Relevance of AMPA receptor-mediated NO signaling
| Autor: | Osamu Hanyu, Charles A. Strott, Hirotoshi Fuda, Atsushi Kohjitani |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Kainic acid
medicine.medical_specialty Glutamic Acid Kainate receptor AMPA receptor Benzothiadiazines Nitric Oxide chemistry.chemical_compound Cell Line Tumor Quinoxalines Internal medicine Excitatory Amino Acid Agonists medicine Animals Steroid sulfotransferase RNA Messenger Receptors AMPA Enzyme Inhibitors Reverse Transcriptase Polymerase Chain Reaction General Neuroscience Glioma Molecular biology Rats Isoenzymes Endocrinology chemistry Pregnenolone NBQX Cyclothiazide Sulfotransferases Pregnenolone sulfate Excitatory Amino Acid Antagonists Neuroglia Signal Transduction medicine.drug |
| Zdroj: | Neuroscience Letters. 430:75-80 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2007.10.023 |
| Popis: | The neurosteroid pregnenolone sulfate (PREGS), which is synthesized in glial cells, plays a significant role in learning and memory performance. The aim of this study was to investigate the regulation of expression of the steroid sulfotransferase SULT2B1a, which catalyzes the conversion of pregnenolone to PREGS, using the rat C6 glioma cell line. Rat C6 glioma cells expressed the SULT2B1a isoform, which sulfonates pregnenolone, but, neither the SULT2B1b isoform, which catalyzes cholesterol, nor the prototypical steroid sulfotransferase SULT2A1 were expressed in these cells. Increasing concentrations of l-glutamic acid in the presence of cyclothiazide, which prevents AMPA receptor desensitization, attenuated SULT2B1a mRNA expression; however, neither NMDA nor kainic acid had a significant effect. Exposure to the synthetic glutamate analogue alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the presence of cyclothiazide also inhibited SULT2B1a expression. Attenuation of SULT2B1a expression by L-glutamic acid was reversed by the selective AMPA/kainate receptor antagonist 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), and partially reversed by the specific neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI). Induction of inducible NOS by TNF-alpha in combination with lipopolysaccharide (LPS) dramatically attenuated SULT2B1a expression; this was partially reversed by the specific inducible NOS inhibitor N(6)-(1-iminoethyl)-L-lysine hydrochloride (L-NIL). Furthermore, exposure to exogenous NO donors inhibited SULT2B1a mRNA expression, and exposure to sodium nitroprusside, LPS/TNF-alpha and L-glutamic acid in combination with cyclothiazide increased the production of nitrite, a stable degradation product of NO. These findings suggest that expression of SULT2B1a, which catalyzes PREGS production, is inhibited by activation of excitatory amino acid receptors of the AMPA subtype, via facilitation of intracellular NO signaling. |
| Databáze: | OpenAIRE |
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