Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The behaviour of the membrane enzymes PIP2-phospholipase C (PLC), that modulates the extracellular signals, and gamma-glutamyltransferase (gamma-GT), involved in metabolite transport, was followed during the early and active phases of apoptosis induced in CCRF-CEM cells by glucocorticoid (10(-6) M dexamethasone, DEX). The activities of gamma-GT and PLC increased significantly at 15 and 30 s after dexamethasone addition. Both activities decreased to the control level after 2 min but increased again at 5 min. The enzyme activities were high in apoptotic cells. Apoptosis was seen after incubation with 10(-6)M dexamethasone for 48 h, with decreased cell number, cellular activation (MTT) and S-phase percentage; enhanced DNA fragmentation and propidium iodide uptake; and ultrastructural changes in the chromatin and cell membranes. The changes in enzyme activity are indicators which occur much earlier than the cellular events related to the apoptotic death in CD4(+)-T CEM lymphoblastoid cells.
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PMID:Changes in the activities of signal transduction and transport membrane enzymes in CEM lymphoblastoid cells by glucocorticoid-induced apoptosis. 778 13

Glucocorticoids have a wide range of effects in mammalian tissues. In this study we investigated the hypothesis that some of the long-term effects of glucocorticoids on immune cell function may occur by regulating phospholipase C (PLC) signal transduction systems that are known to play a role in immune cell activation. PLC activity was measured in vitro with [3H]phosphatidylinositol and [3H]phosphatidylinositol 4,5-bisphosphate as substrates. Although the guanine nucleotide regulatory protein, Gi, is a membrane-associated protein, our unpublished observations show significant Gi levels in the cytosol of several tissues, including the spleen, where the highest levels were detected. We measured cytosolic Gi alpha immunoreactivity after hormone treatment to establish the relationship between the regulation of cytosolic PLC activity and cytosolic Gi alpha levels. GTP and its nonhydrolyzable analogs have been shown in some instances to regulate soluble PLC activity. In vivo administration of dexamethasone (DEX; 5 mg/ml, sc) to rats for 24 h reduced soluble PLC activity from spleen by 25-50%. In the same tissue, cytosolic Gi alpha immunoreactivity was decreased by 60-70%. The time dependency and receptor specificity of the glucocorticoid effects observed in vivo were investigated further in isolated splenocytes. Treatment of intact splenocytes with DEX (10(-8) and 10(-7) M) for 48 h inhibited calcium-stimulated cytosolic PLC activity by 80-90%; cytosolic Gi alpha immunoreactivity was also reduced by about 90%. In a time course experiment with DEX (10(-7) M) in splenocytes, significant effects were apparent by 12 h after steroid treatment and were maximal by 48 h. When splenocytes were coincubated with DEX (10(-8) M) and the glucocorticoid receptor antagonist RU 486 (10(-7) M), the effects of DEX on soluble PLC activity and cytosolic Gi alpha immunoreactivity were both blocked, suggesting that the effects were mediated by DEX activation of the classical intracellular glucocorticoid receptor. The effects of glucocorticoids reported here may represent one way by which these hormones act to modulate immune cell function.
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PMID:Glucocorticoids inhibit soluble phospholipase C activity and cytosolic guanine nucleotide regulatory protein-alpha i immunoreactivity in spleen. 840 43

An increase in glucocorticoid levels and down-regulation of BDNF (brain-derived neurotrophic factor) are supposed to be involved in the pathophysiology of depressive disorders. However, possible crosstalk between glucocorticoid- and BDNF-mediated neuronal functions in the CNS has not been elucidated. Here, we examined whether chronic glucocorticoid exposure influences BDNF-triggered intracellular signaling for glutamate release via a glutamate transporter. We found that chronic exposure to dexamethasone (DEX, a synthetic glucocorticoid) suppressed BDNF-induced glutamate release via weakening the activation of the PLC-gamma (phospholipase C-gamma)/Ca(2+) system in cultured cortical neurons. We demonstrated that the GR (glucocorticoid receptor) interacts with receptor tyrosine kinase for BDNF (TrkB). Following DEX treatment, TrkB-GR interaction was reduced due to the decline in GR expression. Corticosterone, a natural glucocorticoid, also reduced TrkB-GR interaction, BDNF-stimulated PLC-gamma, and BDNF-triggered glutamate release. Interestingly, BDNF-dependent binding of PLC-gamma to TrkB was diminished by DEX. SiRNA transfection to induce a decrease in endogenous GR mimicked the inhibitory action of DEX. Conversely, DEX-inhibited BDNF-activated PLC-gamma signaling for glutamate release was recovered by GR overexpression. We propose that TrkB-GR interaction plays a critical role in the BDNF-stimulated PLC-gamma pathway, which is required for glutamate release, and the decrease in TrkB-GR interaction caused by chronic exposure to glucocorticoids results in the suppression of BDNF-mediated neurotransmitter release via a glutamate transporter.
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PMID:Glucocorticoid receptor interaction with TrkB promotes BDNF-triggered PLC-gamma signaling for glutamate release via a glutamate transporter. 1912 84

Brain-specific microRNAs (miRs) may be involved in synaptic plasticity through the control of target mRNA translation. Brain-derived neurotrophic factor (BDNF) also contributes to the regulation of synaptic function. However, the possible involvement of miRs in BDNF-regulated synaptic function is poorly understood. Importantly, an increase in glucocorticoid levels and the downregulation of BDNF are supposed to be involved in the pathophysiology of depressive disorders. Previously, we reported that glucocorticoid exposure inhibited BDNF-regulated synaptic function via weakening mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 (MAPK/ERK) and/or phospholipase C-gamma (PLC-gamma) intracellular signaling in cultured neurons [Kumamaru et al (2008) Mol Endocrinol 22:546-558; Numakawa et al (2009) Proc Natl Acad Sci U S A 106:647-652]. Therefore, in this study, we investigate the possible influence of glucocorticoid on BDNF/miRs-stimulated biological responses in cultured cortical neurons. Significant upregulation of miR-132 was caused by BDNF, although miR-9, -124, -128a, -128b, -134, -138, and -16 were intact. Transfection of exogenous ds-miR-132 induced marked upregulation of glutamate receptors (NR2A, NR2B, and GluR1), suggesting that miR-132 has a positive effect on the increase in postsynaptic proteins levels. Consistently, transfection of antisense RNA to inhibit miR-132 function decreased the BDNF-dependent increase in the expression of postsynaptic proteins. U0126, an inhibitor of the MAPK/ERK pathway, suppressed the BDNF-increased miR-132, suggesting that BDNF upregulates miR-132 via the MAPK/ERK1/2 pathway. Interestingly, pretreatment with glucocorticoid (dexamethasone, DEX) reduced BDNF-increased ERK1/2 activation, miR-132 expression, and postsynaptic proteins. We demonstrate that the exposure of neurons to an excess glucocorticoid results in a decrease in the BDNF-dependent neuronal function via suppressing miR-132 expression.
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PMID:Glucocorticoid attenuates brain-derived neurotrophic factor-dependent upregulation of glutamate receptors via the suppression of microRNA-132 expression. 1995 14