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Quercetin is a flavonol polyphenol widely found in many vegetables, grains and fruits. Quercetin has been shown to inhibit proliferation and invasion of various glioma cells, and is regarded as a potential anticancer agent against glioma. However, whether and how this drug could affect brain blood vessels and endothelial cells are less understood. Further, there is hitherto no report on how quercetin affects brain endothelial cell (EC) Ca homeostasis. In this report we investigated the effects of quercetin on Ca homeostasis in mouse brain bEND.3 EC. We demonstrated that quercetin raised cytosolic Ca level in a concentration-dependent manner. Quercetin-triggered Ca signal composed of both internal Ca release and extracellular Ca influx. Quercetin caused Ca release from the endoplasmic reticulum, and consistently, inhibition of inositol 1,4,5-trisphosphate receptor (IP3R) by xestospongin C (XeC) suppressed quercetin-triggered Ca release. Quercetin also caused Ca release from lysosomes, an observation in concordance with the inhibition of quercetin-triggered Ca release by trans-Ned-19, a blocker of two-pore channels (TPC). As quercetin depleted intracellular Ca storage, it suppressed ATP-induced Ca release and thereby blunted ATP-triggered Ca signaling. In addition, quercetin co-treatment significantly suppressed ATP-stimulated nitric oxide (NO) release. Our work therefore showed, for the first time, quercetin perturbed intracellular Ca stores and strongly suppressed ATP-triggered response in bEND.3 cells.
This article was published in the following journal.
Name: Fundamental & clinical pharmacology
In a previous publication when we studied the purinergic receptor with which ATP interacted in mouse brain bEND.3 endothelial cells, we observed addition of 3 μM AR-C 118925XX (ARC; selective P2Y ant...
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Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.
A drug formerly used in the treatment of angina pectoris but superseded by less hazardous drugs. Prenylamine depletes myocardial catecholamine stores and has some calcium channel blocking activity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1406)
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
CELL CYCLE regulatory signaling systems that are triggered by DNA DAMAGE or lack of nutrients during G2 PHASE. When triggered they restrain cells transitioning from G2 phase to M PHASE.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...