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Enzyme
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Target Concepts:
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Query: EC:1.14.16.2 (
tyrosine hydroxylase
)
14,760
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sodium arsenite
and osmotic shock both stimulated stress-activated protein kinase-2 (SAPK2, also termed RK, p38, CSBP and Mxi2) and its downstream target mitogen-activated protein kinase (MAP kinase)-activated protein kinase-2 (MAPKAP-K2) in bovine adrenal chromaffin and rat PC12 cells. The same stimuli also increased
tyrosine hydroxylase
activity 2-3-fold and induced its phosphorylation at Ser19, a residue phosphorylated by MAPKAP-K2 in vitro. The arsenite-induced activation of
tyrosine hydroxylase
and its phosphorylation at Ser19 were prevented by SB 203580 at concentrations similar to those that inhibited SAPK2 in vitro. These results indicate that MAPKAP-K2 mediates the stress-induced activation of
tyrosine hydroxylase
. SB 203580 had no effect on the phosphorylation or activation of
tyrosine hydroxylase
induced by nerve growth factor or forskolin, which trigger the phosphorylation of Ser31 and Ser40, respectively. Stimulation of bovine adrenal chromaffin cells with acetylcholine activated SAPK2 and MAPKAP-K2, as well as p42/p44 MAP kinases and their downstream target MAPKAP-K1. The half-times for activation of MAPKAP-K1 and MAPKAP-K2 (1 min) were similar. In contrast, the activation of
tyrosine hydroxylase
by acetylcholine peaked within 1 min and gradually declined thereafter. Neither SB 203580 (which blocked the activation of MAPKAP-K2 by acetylcholine) nor PD 98059 (which prevented the activation of p42/p44 MAP kinases by acetylcholine) affected
tyrosine hydroxylase
activation after 1 min, but these compounds inhibited activation by 40-50% after 5 min. PD 98059 prevented the acetylcholine-induced phosphorylation of
tyrosine hydroxylase
at Ser31, the residue targetted by p42/p44 MAP kinases in vitro, but did not inhibit the phosphorylation of Ser40 (which is phosphorylated by MAPKAP-K1 in vitro). Our results establish that p42/p44 MAP kinases mediate the acetylcholine-induced phosphorylation of
tyrosine hydroxylase
at Ser31. SB 203580 did not suppress the phosphorylation of Ser19 or Ser40 by acetylcholine but, like PD 98059, this drug decreased the phosphorylation of Ser31. SAPK2 may therefore contribute to the acetylcholine-induced activation of
tyrosine hydroxylase
by facilitating (in an unknown way) its phosphorylation by MAP kinases.
...
PMID:Participation of a stress-activated protein kinase cascade in the activation of tyrosine hydroxylase in chromaffin cells. 928 46
Although exposure to arsenic (As) induces neurotoxic changes, there is a lack of data regarding its specific effects on neurotransmission, particularly dopaminergic neurotransmission. In this study, the dopamine content and expression of
tyrosine hydroxylase
(TH) and dopamine receptors (DRs) were examined in the striatum and cerebral cortex of the mouse brain following the administration of As (1-100 mg/L
NaAsO2
in drinking water). After 3 weeks, significantly decreased TH expression and dopamine content, both in the striatum and the cerebral cortex of mice treated with 100 mg/L As, were observed when compared with controls. Although DR expression was similar in the cerebral cortex of As-treated mice, DRD1 to DRD4 expression significantly increased in the striatum of 100 mg/L As-exposed mice. These data indicate that altered dopaminergic neurotransmission may contribute to As-induced neurotoxic effects.
...
PMID:Arsenic exposure in drinking water alters the dopamine system in the brains of C57BL/6 mice. 2531 7
