MCU-i4, a mitochondrial Ca uniporter modulator, induces breast cancer BT474 cell death by enhancing glycolysis, ATP production and reactive oxygen species (ROS) burst.

Objectives: Mitochondrial Ca uniporter (MCU) provides a Ca influx pathway from the cytosol into the mitochondrial matrix and a moderate mitochondrial Ca rise stimulates ATP production and cell growth. MCU is highly expressed in various cancer cells including breast cancer cells, thereby increasing the capacity of mitochondrial Ca uptake, ATP production, and cancer cell proliferation. The objective of this study was to examine MCU inhibition as an anti-cancer mechanism.

CDN1163, a SERCA activator, causes intracellular Ca leak, mitochondrial hyperpolarization and cell cycle arrest in mouse neuronal N2A cells.

Objective: Activity or expression of sarcoplasmic/endoplasmic reticulum Ca ATPase (SERCA) is diminished in some disease states such as cardiac failure and diabetes mellitus. A newly developed activator of SERCA, CDN1163, reportedly rescued or alleviated pathological conditions attributed to dysfunctional SERCA. We examined whether CDN1163 could relieve mouse neuronal N2A cell growth inhibition caused by cyclopiazonic acid (CPA, SERCA inhibitor).

Afatinib triggers a Ni -resistant Ca influx pathway in A549 non-small cell lung cancer cells.

Afatinib is used to treat non-small cell lung cancer cells (NSCLC), and its mechanism involves irreversible inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase. In this study, we examined if afatinib had cytotoxic action against NSCLC other than inhibition of tyrosine kinase. Afatinib (1-30 μM) caused apoptotic death in A549 NSCLC in a concentration-dependent manner.

Suppression of Ca oscillations by SERCA inhibition in human alveolar type 2 A549 cells: rescue by ochratoxin A but not CDN1163.

Aims: Lung type 2 alveolar cells, by secreting surfactant to lower surface tension, contribute to enhance lung compliance. Stretching, as a result of lung expansion, triggers type 1 alveolar cell to release ATP, which in turn stimulates Ca-dependent surfactant secretion by neighboring type 2 cells. In this report, we studied ATP-triggered Ca signaling in human alveolar type 2 A549 cells.

Propofol Causes Sustained Ca2+ Elevation in Endothelial Cells by Stimulating Ryanodine Receptor and Suppressing Plasmalemmal Ca2+ Pump.

Propofol, a general anesthetic administered intravenously, may cause pain at the injection site. The pain is in part due to irritation of vascular endothelial cells. We here investigated the effects of propofol on Ca2+ transport and pain mediator release in human umbilical vein endothelial cells (EA.

A basal level of γ-linolenic acid depletes Ca stores and induces endoplasmic reticulum and oxidative stresses to cause death of breast cancer BT-474 cells.

Gamma-linolenic acid (GLA), a natural fatty acid obtained from oils of various vegetables and seeds, has been demonstrated as an anticancer agent. In this work, we investigated the anticancer effects of GLA on breast cancer BT-474 cells. GLA at 30 μM, a concentration reportedly within the range of circulating concentrations in clinical studies, caused apoptotic cell death.

Perturbation of Ca stores and store-operated Ca influx by lidocaine in neuronal N2A and NG108-15 cells.

In this report we examined the effects of lidocaine on Ca homeostasis of neuronal cells using microfluorimetric measurement of cytosolic Ca with fura 2 as probe. In mouse neuroblastoma N2A cells, 10 mM lidocaine caused Ca release from the cyclopiazonic acid (CPA)-dischargeable pool and abolished ATP-triggered Ca release. Lidocaine-triggered Ca release was not affected by xestospongin C (XeC), an inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor.

Quercetin depletes intracellular Ca stores and blunts ATP-triggered Ca signaling in bEnd.3 endothelial cells.

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 (EC) are less understood.

Antagonism of Ca-sensing receptors by NPS 2143 is transiently masked by p38 activation in mouse brain bEND.3 endothelial cells.

Ca-sensing receptors (CaSR) are G protein-coupled receptors which are activated by a rise in extracellular Ca. CaSR activation has been known to inhibit parathyroid hormone release and stimulate calcitonin release from parathyroid glands and thyroid parafollicular C cells, respectively. The roles of CaSR in other cell types including endothelial cells (EC) are much less understood.

Gossypol stimulates opening of a Ca - and Na -permeable but Ni - and Co -impermeable pore in bEND.3 endothelial cells.

Gossypol, a polyphenolic dialdehyde toxin isolated from cotton seed, has anti-cancer properties and has recently shown some success in the treatment of glioma. Its effects on brain neurons and blood vessels are poorly understood. In this work we examined the effects of gossypol on cytosolic Ca concentration ([Ca ] ) of mouse brain bEND.

Lobeline improves acute lung injury via nuclear factor-κB-signaling pathway and oxidative stress.

Acute lung injury (ALI) is a severe, life-threatening medical condition whose pathogenesis is linked to neutrophil infiltration of the lung. Activation and recruitment of neutrophils to the lung is mostly attributed to the production of chemokines NO, IL-6, for instance. This study aims to investigate lobeline ability in reducing NO production, and nitric oxide synthase (iNOs) expression.

Inhibition of cytochrome P450 2C9 expression and activity in vitro by allyl isothiocyanate.

The growing interest in the use of natural herbal products and dietary supplements to treat and prevent diseases raises the question of medicinal drug safety. Allyl isothiocyanate, a hydrolysis product of a glucosinolate, sinigrin, has multiple beneficial properties, and based on this fact, allyl isothiocyanate-containing dietary supplements have been developed. To date, no studies of the effects of this compound on the cytochrome P450 2C9 have been reported.

Allyl isothiocyanate (AITC) inhibits pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation and protects against acetaminophen- and amiodarone-induced cytotoxicity.

Antagonizing the action of the pregnane X receptor (PXR) may have important clinical implications for preventing inducer-drug interactions and improving therapeutic efficacy. We identified a widely distributed isothiocyanate, allyl isothiocyanate (AITC), which acts as an effective antagonist of the nuclear receptor pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3). HepG2 cells were used to assay reporter function, mRNA levels, and protein expression.

Genetic variation in NOS2A is associated with a sustained virological response to peginterferon plus ribavirin therapy for chronic hepatitis C in Taiwanese Chinese.

This study aimed to evaluate whether genetic polymorphisms of the inducible nitric oxide synthase (iNOS) gene NOS2A could be associated with a sustained virological response (SVR) among patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2) who were treated with peginterferon plus ribavirin (PEG-IFNα-RBV). We analyzed the associations between SVR to PEG-IFNα-RBV therapy and two single nucleotide polymorphisms (SNPs) in NOS2A. This study included Taiwanese Chinese patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) with or without a SVR.