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The role of tetrahydrobiopterin and catecholamines in the developmental regulation of tyrosine hydroxylase level in the brain
Author(s) -
Homma Daigo,
Katoh Setsuko,
Tokuoka Hirofumi,
Ichinose Hiroshi
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12287
Subject(s) - tetrahydrobiopterin , tyrosine hydroxylase , dopamine , endocrinology , medicine , tyrosine , biopterin , hyperphenylalaninemia , period (music) , enzyme , biology , chemistry , cofactor , biochemistry , phenylalanine , amino acid , physics , acoustics
Tyrosine hydroxylase ( TH ) is a rate‐limiting enzyme for dopamine synthesis and requires tetrahydrobiopterin ( BH 4) as an essential cofactor. BH 4 deficiency leads to the loss of TH protein in the brain, although the underlying mechanism is poorly understood. To give insight into the role of BH 4 in the developmental regulation of TH protein level, in this study, we investigated the effects of acute and subchronic administrations of BH 4 or dopa on the TH protein content in BH 4‐deficient mice lacking sepiapterin reductase. We found that BH 4 administration persistently elevated the BH 4 and dopamine levels in the brain and fully restored the loss of TH protein caused by the BH 4 deficiency in infants. On the other hand, dopa administration less persistently increased the dopamine content and only partially but significantly restored the TH protein level in infant BH 4‐deficient mice. We also found that the effects of BH 4 or dopa administration on the TH protein content were attenuated in young adulthood. Our data demonstrate that BH 4 and catecholamines are required for the post‐natal augmentation of TH protein in the brain, and suggest that BH 4 availability in early post‐natal period is critical for the developmental regulation of TH protein level.