Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-Methyl-4-phenylpyridinium ion (MPP+), a reaction product of a neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was found to inhibit aromatic L-aminoacid decarboxylase activity in rat clonal pheochromocytoma PC12h cells. The enzyme activity was enhanced to several folds by addition of a cofactor, pyridoxal phosphate, and MPP+ inhibited the enhancement of the activity by exogenously added pyridoxal phosphate. The inhibition was competitive to pyridoxal phosphate, and the Ki value of MPP+ was 26.7 +/- 0.4 microM, while the Km value of pyridoxal phosphate was 0.645 +/- 0.053 microM. The inhibition was partly irreversible. The enzyme sample was incubated with MPP+ and then dialyzed against phosphate buffer. After dialysis, the inhibited enzyme activity was only partly recovered by addition of pyridoxal phosphate, even though MPP+ was completely removed. Activity of other enzymes, tyrosine hydroxylase and monoamine oxidase could be recovered by dialysis. On the other hand, MPP+ did not affect the binding of the enzyme with the substrate, L-DOPA or 5-hydroxytryptophan.
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PMID:Inhibition of aromatic L-aminoacid decarboxylase in clonal pheochromocytoma PC12h cells by N-methyl-4-phenylpyridinium ion (MPP+). 325 44

Isolation and propagation of neural stem cells derived from human brain tissue uniquely enables the study of human neurogenesis in vitro. In addition, ex vivo-expanded human neural stem/precursor cells (NPCs) may offer novel therapeutic strategies. We investigated the effects of extracellular nucleotides on the proliferation and differentiation of human mesencephalic neural stem/precursor cells (hmNPCs). When combined with the mitogens epidermal growth factor and fibroblast growth factor 2, UTP (1 microm) boosted proliferation of hmNPCs as shown by increased expression of the proliferation marker proliferating cell nuclear antigen (330%). UTP-induced proliferation was abrogated by the preferential P2Y receptor blocker pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). UTP also stimulated dopaminergic differentiation. Treatment with UTP (100 microm) increased the number of tyrosine hydroxylase (TH)-positive cells and TH protein by 267 and 319% respectively. UTP-stimulated dopaminergic differentiation of hmNPCs was blocked by the P2 receptor antagonists suramin (10 microm) and PPADS (100 microm). In addition, UDP (1 microm) enhanced TH protein expression by 194%. During differentiation, treatment with UTP stimulated the extracellular signal-regulated kinase (ERK) pathway. Both ERK1/2 phosphorylation and dopaminergic differentiation were inhibited by U0126, a selective ERK kinase inhibitor, as well as by suramin. When other P2 receptor agonists (ATP, ADP and adenosine 5'-O-(2-thiophosphate) (ADPbetaS); all 100 microm) were applied, both proliferation and dopaminergic differentiation of NPCs were compromised. We conclude that uracil nucleotides exert specific P2 receptor-mediated effects on midbrain-derived human NPCs, and may be used to enhance both proliferation and dopaminergic differentiation.
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PMID:Uracil nucleotides stimulate human neural precursor cell proliferation and dopaminergic differentiation: involvement of MEK/ERK signalling. 1707 58