Recently we showed that phosphorylated tyrosine hydroxylase (TH) at Ser40 (p40-TH) was degradated by ubiquitin proteasome system (UPS) and easily insolubilized, and that TH level was decreased in the striatum of tetrahydrobiopterin (BH4) deficient mice. Here we studied the effect of depletion of dopamine (DA) or BH4 to the regulation of the amount of p40-TH. We treated PC12D cells with quinpirole or haloperidol, NSD-1015; an inhibitor of aromatic aminoacid decarboxylase (AADC), or DAHP; an inhibitor of GTP cyclohydrolase I (GCH). The amount of p40-TH was measured by western blotting. Treatment with haloperidol induced the short and transient elevation of p40-TH level (30 min), and exposure to NSD-1015 or DAHP induced the long-lasting elevation of p40-TH after 48 h. We are also examining the effects using primary mesencephalic neurons. The molecular mechanism of long-lasting elevation of p40-TH by DA deficiency is now under investigation.
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