Reduction of enzyme activity of tyrosine hydroxylase and aromatic L-aminoacid decarboxylase in clonal pheochromocytoma PC12h cells by carcinogenic heterocyclic amines.
Out of carcinogenic heterocyclic amines, which are produced by pyrolysis of tryptophan in food, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) were found to reduce the activity of enzymes related to catecholamine metabolism in clonal rat pheochromocytoma PC12h cells. By 6 days' culture in the presence of 10 nM to 10 microM Typ-P-1 and -2, these heterocyclic amines were accumulated in the cells, and activity of tyrosine hydroxylase (TH) and aromatic L-aminoacid decarboxylase (AADC) were reduced markedly. Reduction of these enzyme activity was observed with Trp-P-1 and -2 at the concentrations lower than 1 microM, while cell protein and enzyme activity of a non-specific enzyme, beta-galactosidase were reduced only with 10 microM Trp-P-1. These results show that these heterocyclic amines are neurotoxins specific for dopaminergic neurons.
Naoi
M
M
Department of Biochemistry, Nagoya University School of Medicine, Japan.
Takahashi
T
T
Ichinose
H
H
Wakabayashi
K
K
Sugimura
T
T
Nagatsu
T
T
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D010673:Pheochromocytoma; D051381:Rats; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D002243:Carbolines; D002395:Catecholamines; D009419:Nerve Tissue Proteins; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D001616:beta-Galactosidase; D001142:Aromatic-L-Amino-Acid Decarboxylases; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole