Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serotonin metabolite 5-hydroxytryptophol was studied in human cerebrospinal fluid. A minor fraction (approximately 13%) was found in conjugated form from which it was liberated by treatment with sulphatase containing beta-glucuronidase activity. A concentration gradient of 5-hydroxytryptophol concentration was shown on lumbar tapping and the concentration in ventricular CSF was about 2.5 times higher than that in lumbar CSF. 5-Hydroxytryptophol and 5-hydroxyindoleacetic acid concentrations were significantly correlated in healthy, psychotic, and depressed subjects, but not in alcoholics. 5-Hydroxytryptophol concentrations in CSF of psychotic and depressed subjects were not different from those of healthy controls (4.22 pmol/ml +/- 0.15, SEM). In healthy subjects, hereditary factors seemed to have little influence on the CSF level of 5-hydroxytryptophol.
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PMID:5-hydroxytryptophol in human cerebrospinal fluid: conjugation, concentration gradient, relationship to 5-hydroxyindoleacetic acid, and influence of hereditary factors. 620 46

It is known that RGS9-2 gene knockout mice show supersensitivity to DA and have a marked elevation in the proportion of DA D2 receptors in the high-affinity state for DA (D2(High) receptors). As this is a similar profile to that observed in the CNS from subjects with schizophrenia, we examined whether postmortem CNS tissue from subjects with the disorder and brain striata from an animal model of psychosis or schizophrenia (the amphetamine-sensitized rat) had altered levels of RGS9-2. The mRNA for RGS9-2 in 29 control hippocampi was 0.185 +/- 0.015 fg per fg of beta-glucuronidase mRNA (average +/- SE), while that in 29 schizophrenia hippocampi was 0.145 +/- 0.015 fg per fg of beta-glucuronidase mRNA (average +/- SE), a reduction of 22%. Of the many receptor-regulating genes related to G proteins, and of 11 RGS genes, RGS9-2 was the most reduced in the amphetamine-sensitized rat striatum. The reduced levels of RGS9-2 expression in both an animal model of schizophrenia and a postmortem schizophrenia brain provide further evidence implicating RGS9-2 as a candidate gene in schizophrenia.
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PMID:Consistent with dopamine supersensitivity, RGS9 expression is diminished in the amphetamine-treated animal model of schizophrenia and in postmortem schizophrenia brain. 1731 83

Recent studies have shown that the elevation in calcium/calmodulin-dependent protein kinase II (CaMKII) may play an important role in amphetamine-induced dopamine release, as well as in the increase of dopamine D2 receptor high-affinitystates in psychosis. Because amphetamine sensitization is a widely used animal model of psychosis or schizophrenia, we investigated whether amphetamine sensitization results in an overall increase in the alpha and beta subunits of CaMKII. To answer this question, we measured CaMKII alpha and beta subunit mRNA expression using Real-Time Quantitative PCR in amphetamine-sensitized rat striata, compared to saline-treated controls. The results were then standardized to beta-glucuronidase, a housekeeping gene. Our results showed a statistically significant increase in the CaMKII beta subunit, and an increase in the alpha subunit which did not reach statistical significance. Because the levels of both CaMKIIbeta and CaMKIIalpha play a role in neuronal function and synapse formation, the present finding of an elevated level of CaMKII beta and alpha subunit mRNA in the amphetamine-sensitized model of psychosis points to the possibility of dysregulated levels of CaMKII subunits in human psychosis.
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PMID:Amphetamine sensitization elevates CaMKIIbeta mRNA. 1760 7