Ascorbic acid stimulates DOPA synthesis and tyrosine hydroxylase gene expression in the human neuroblastoma cell line SK-N-SH.
Ascorbic acid is well known to induce noradrenaline synthesis in sympathetic nervous cells. In a series of experiments we found that incubation of the neuroblastoma cell line SK-N-SH with ascorbic acid (100-500 microM) for 2 h results in a significantly enhanced synthesis of 3,4-dihydroxyphenylalanine (DOPA) and dopamine. Additionally, cDNA-polymerase chain reaction (cDNA-PCR) analysis of relative mRNA levels corresponding to the enzymes involved in catecholamine synthesis revealed a 3-fold increase of tyrosine hydroxylase gene expression after 5 days of incubation with ascorbic acid (200 microM), whereas expression of dopamine-beta-hydroxylase was found to be unaltered. In summary the data give evidence that ascorbic acid leads to enhanced DOPA production in SK-N-SH cells by two different mechanisms: at the metabolic level after short-term incubation and by increasing the tyrosine hydroxylase gene expression after long-term incubation. Based on these data we suppose that enhancement of DOPA synthesis by ascorbic acid may be useful in the treatment of early Parkinson's disease.
Seitz
G
G
Department of Hematology and Oncology, Children's Hospital, University of Tübingen, Germany.
Gebhardt
S
S
Beck
J F
JF
Böhm
W
W
Lode
H N
HN
Niethammer
D
D
Bruchelt
G
G
D001205:Ascorbic Acid / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics*
D002395:Catecholamines; D012333:RNA, Messenger; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D001205:Ascorbic Acid