Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are many clinical and experimental reports demonstrating that estrogens and insulin interact when affecting their target organs. Estrogen receptors consist of two isoforms, estrogen receptors-alpha (ER-alpha) and -beta (ER-beta), but their roles in insulin-induced glucose uptake in mature adipose tissue have yet to be clarified. To evaluate the roles of ER-alpha, expressed predominantly in adipocytes, we have investigated the effects of estradiol (E2), an ER-alpha selective agonist (PPT), and its selective antagonist (MPP) on glucose uptake and insulin action in 3T3-L1 adipocytes. 3T3-L1 adipocytes were exposed to E2 or PPT and/or MPP at different concentrations. The cells were then subjected to 2-deoxy-D-glucose transport assay, western blot analysis, or RT-PCR analysis. Treatment of these cells with E2 or PPT resulted in biphasic effects on glucose transport, that is high (10(-5) M or 3 x 10(-6) M each) and low (10(-8) M) doses produced inhibition and stimulation, respectively. The favorable effect observed at 10(-8) M of E2 was diminished by treatment with MPP. Western bolt analysis revealed that these effects of E2, PPT and MPP paralleled the level of IRS-1 tyrosine phosphorylation. However, IRS-1 serine phosphorylation, suppressor of cytokine signaling (SOCS)-1,-2,-3 and protein tyrosine phosphatase 1B (PTP1B) expression did not change compared to control subjects. Our data clearly show that ER-alpha contributes to insulin stimulated glucose uptake through regulation of the tyrosine phosphorylation of IRS-1 protein.
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PMID:Estrogen receptor alpha regulates insulin sensitivity through IRS-1 tyrosine phosphorylation in mature 3T3-L1 adipocytes. 1700 Nov 8

Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), on metabotropic glutamate receptor 1/5 agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced hippocampal synaptic plasticity, and MPP+ incubation blocked DHPG-induced hippocampal long-term depression (LTD) in Schaffer collateral-CA1 synapses. Our further findings indicated that, this blockage was reversed by pre-application of calpain inhibitor III, but not by cathepsin inhibitors. Biochemical analysis showed that MPP+ treatment stimulated calpain activation, displayed by spectrin breakdown. Interestingly, the level and activity of protein tyrosine phosphatase 1B (PTP1B) were reduced after MPP+ incubation and the decrease of PTP1B was prohibited by calpain inhibitor III. In addition, PTP1B inhibitor also blocked DHPG-induced LTD, mimicking the effect of MPP+. In summary, our data implicated that MPP+ activated calpain-dependent PTP1B degradation, which subsequently impaired hippocampal LTD. This novel effect of MPP+ might partially explain the impairment of memory processing in the pathogenesis of PD.
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PMID:MPP+ inhibits mGluR1/5-mediated long-term depression in mouse hippocampus by calpain activation. 2790 90