NSD-1015 alters the gene expression of aromatic L-amino acid decarboxylase in rat PC12 pheochromocytoma cells.
Aromatic L-amino acid decarboxylase (AADC) is involved in the synthesis of the putative neurotransmitters dopamine (DA), 5-hydroxytryptamine (5-HT), and trace amines some of which have been proposed as neuromodulators, such as 2-phenylethylamine and tryptamine. We report here that the gene expression of AADC can be regulated by the AADC inhibitor NSD-1015 in PC12 cells. The cells were treated with different doses of NSD-1015 (0.01-10 microM) for 3 days. Slot blot hybridization was performed to detect AADC mRNA and Western immunoblot to detect AADC protein. The cDNA probe for rat AADC was generated by reverse transcription from rat adrenal gland total RNA and was amplified by the polymerase chain reaction (PCR) method. The results demonstrated that NSD-1015 produced a concentration-dependent up-regulation in AADC mRNA levels which is followed by a stable increase in AADC protein. The results suggest that AADC is an enzyme that can be regulated at the level of gene expression. The finding may be of importance in the study of DA transmission and for an improved understanding of this enzyme.
Li
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XM
Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
Juorio
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AV
Boulton
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AA
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics*; D015153:Blotting, Western; D015342:DNA Probes; D015870:Gene Expression / Q000187:drug effects*; D006834:Hydrazines / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D016716:PC12 Cells / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D015342:DNA Probes; D006834:Hydrazines; D012333:RNA, Messenger; C004297:3-hydroxybenzylhydrazine; D001142:Aromatic-L-Amino-Acid Decarboxylases