Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Albinism is a genetic defect characterized by a loss of pigmentation. The neurosensory retina, which is not pigmented, exhibits pathologic changes secondary to the loss of pigmentation in the retina pigment epithelium (RPE). How the loss of pigmentation in the RPE causes developmental defects in the adjacent neurosensory retina has not been determined, but offers a unique opportunity to investigate the interactions between these two important tissues. One of the genes that causes albinism encodes for an orphan GPCR (OA1) expressed only in pigmented cells, including the RPE. We investigated the function and signaling of OA1 in RPE and transfected cell lines. Our results indicate that OA1 is a selective L-DOPA receptor, with no measurable second messenger activity from two closely related compounds, tyrosine and dopamine. Radiolabeled ligand binding confirmed that OA1 exhibited a single, saturable binding site for L-DOPA. Dopamine competed with L-DOPA for the single OA1 binding site, suggesting it could function as an OA1 antagonist. OA1 response to L-DOPA was defined by several common measures of G-protein coupled receptor (GPCR) activation, including influx of intracellular calcium and recruitment of beta-arrestin. Further, inhibition of tyrosinase, the enzyme that makes L-DOPA, resulted in decreased PEDF secretion by RPE. Further, stimulation of OA1 in RPE with L-DOPA resulted in increased PEDF secretion. Taken together, our results illustrate an autocrine loop between OA1 and tyrosinase linked through L-DOPA, and this loop includes the secretion of at least one very potent retinal neurotrophic factor. OA1 is a selective L-DOPA receptor whose downstream effects govern spatial patterning of the developing retina. Our results suggest that the retinal consequences of albinism caused by changes in melanin synthetic machinery may be treated by L-DOPA supplementation.
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PMID:L-DOPA is an endogenous ligand for OA1. 2007 24

Transplantation of retinal pigment epithelial (RPE) cells in the basal ganglia has been proposed as a novel cell-based therapy for Parkinson's disease (PD), by providing a constant source of dopamine replacement via the melanin synthetic pathway enzyme tyrosinase. We have demonstrated previously that human RPE cells also produce a neurotrophic effect on primary cultures of rat striata mesencephalic (dopaminergic) neurons and showed that pigment epithelium derived factor (PEDF) accounted for a major portion of the neurotrophic effect. We now have also begun studies that demonstrate that the neurotrophic effect of PEDF corresponds to neuroprotection against toxins used to produce experimental PD. This was shown in (1) rotenone and (2) 6-hydroxydopamine (6-OHDA) in vitro models. The toxins were added at day 10 in culture, PEDF was added 1h prior. The cultures were fixed and analyzed after tyrosine hydroxylase (TH) immunocytochemical staining. Cell count of TH+ neurons clearly shows the neuroprotective potential of PEDF in both neurotoxin models. The neurotoxic effect of rotenone (25nM) on dopaminergic neurons is reversed by addition of PEDF. At a concentration of 1ng/ml PEDF the neurotoxic effect of rotenone is completely counteracted. PEDF (1ng/ml) has also a neuroprotective effect in the 6-OHDA midbrain in vitro model. The effect is most pronounced at concentrations of 25microM and 50microM 6-OHDA. We conclude that the neurotrophic factor PEDF, produced from RPE cells, can improve neuronal survival in models of PD, and plan to test if this effect can be observed using in vivo models of PD following RPE transplantation.
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PMID:Pigment epithelium derived factor (PEDF) is neuroprotective in two in vitro models of Parkinson's disease. 1944 75

Here, polycythemia vera (PV)-related genes were screened by the Online Mendelian Inheritance in Man (OMIM), and literature pertaining to the identified genes was extracted and a protein-protein interaction network was constructed using various Cytoscape plugins. Various molecular complexes were detected using the Clustervize plugin and a gene ontology-enrichment analysis of the biological pathways, molecular functions, and cellular components of the selected molecular complexes were identified using the BiNGo plugin. Fifty-four PV-related genes were identified in OMIM. The protein-protein interaction network contains 5 molecular complexes with correlation integral values >4. These complexes regulated various biological processes (peptide tyrosinase acidification, cell metabolism, and macromolecular biosynthesis), molecular functions (kinase activity, receptor binding, and cytokine activity), and the cellular components were mainly concentrated in the nucleus, intracellular membrane-bounded organelles, and extracellular region. These complexes were associated with the JAK-STAT signal transduction pathway, neurotrophic factor signaling pathway, and Wnt signaling pathway, which were correlated with chronic myeloid leukemia and acute myeloid leukemia.
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PMID:Construction of polycythemia vera protein interaction network and prediction of related biological functions. 2690 22