The level of nitric oxide regulates lipocalin-2 expression under inflammatory condition in RINm5F beta-cells.

We previously reported that proinflammatory cytokines (interleukin-1β and interferon-γ) induced the expression of lipocalin-2 (LCN-2) together with inducible nitric oxide synthase (iNOS) in RINm5F beta-cells. Therefore, we examined the effect of nitric oxide (NO) on LCN-2 expression in cytokines-treated RINm5F beta-cells. Additionally, we observed the effect of LCN-2 on cell viability.

Induction mechanism of lipocalin-2 expression by co-stimulation with interleukin-1β and interferon-γ in RINm5F beta-cells.

Lipocalin-2 (LCN-2) was known to play a role in obesity and insulin resistance, however, little is known about the expression of LCN-2 in pancreatic islet β-cells. We examined the molecular mechanisms by which proinflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ) induce LCN-2 expression in RINm5F β-cells. IL-1β significantly induced LCN-2 expression while IFN-γ alone did not induce it.

Exendin-4 inhibits iNOS expression at the protein level in LPS-stimulated Raw264.7 macrophage by the activation of cAMP/PKA pathway.

Glucagon-like peptide-1 (GLP-1) and its potent agonists have been widely studied in pancreatic islet β-cells. However, GLP-1 receptors are present in many extrapancreatic tissues including macrophages, and thus GLP-1 may have diverse actions in these tissues and cells. Therefore, we examined the mechanism by which exendin-4 (EX-4), a potent GLP-1 receptor agonist, inhibits lipopolysaccharide (LPS)-induced iNOS expression in Raw264.

Cholinergic induction of input-specific late-phase LTP via localized Ca2+ release in the visual cortex.

Acetylcholine facilitates long-term potentiation (LTP) and long-term depression (LTD), substrates of learning, memory, and sensory processing, in which acetylcholine also plays a crucial role. Ca(2+) ions serve as a canonical regulator of LTP/LTD but little is known about the effect of acetylcholine on intracellular Ca(2+) dynamics. Here, we investigated dendritic Ca(2+) dynamics evoked by synaptic stimulation and the resulting LTP/LTD in layer 2/3 pyramidal neurons of the rat visual cortex.

Effects of physiological quercetin metabolites on interleukin-1β-induced inducible NOS expression.

Cytokines released by inflammatory cells around the pancreatic islets are implicated in the pathogenesis of diabetes mellitus. Specifically, interleukin-1β (IL-1β) is known to be involved in islet β-cell damage by activation of nuclear factor-κB (NF-κB)-mediated inducible nitric oxide synthase (iNOS) gene expression. Though most flavonoids are shown to have various beneficial effects, little is known about the anti-inflammatory effects of their metabolites.

Molecular mechanisms of early growth response protein-1 (EGR-1) expression by quercetin in INS-1 beta-cells.

Early growth response-1 (EGR-1), one of immediate early response genes, is involved in diverse cellular response. We recently reported that quercetin increased catalytic subunit of γ-glutamylcysteine ligase (GCLC) via the interaction of EGR-1 to GCLC promoter in INS-1 beta-cells. Therefore, this study investigated molecular mechanisms of quercetin-induced EGR-1 expression in INS-1 cells.

Grape seed proanthocyanidin extract inhibits glutamate-induced cell death through inhibition of calcium signals and nitric oxide formation in cultured rat hippocampal neurons.

Background: Proanthocyanidin is a polyphenolic bioflavonoid with known antioxidant activity. Some flavonoids have a modulatory effect on [Ca²⁺]i. Although proanthocyanidin extract from blueberries reportedly affects Ca²⁺ buffering capacity, there are no reports on the effects of proanthocyanidin on glutamate-induced [Ca²⁺]i or cell death.

Octyl Gallate Inhibits ATP-induced Intracellular Calcium Increase in PC12 Cells by Inhibiting Multiple Pathways.

Phenolic compounds affect intracellular free Ca(2+) concentration ([Ca(2+)](i)) signaling. The study examined whether the simple phenolic compound octyl gallate affects ATP-induced Ca(2+) signaling in PC12 cells using fura-2-based digital Ca(2+) imaging and whole-cell patch clamping. Treatment with ATP (100 microM) for 90 s induced increases in [Ca(2+)](i) in PC12 cells.

Quercetin-induced upregulation of human GCLC gene is mediated by cis-regulatory element for early growth response protein-1 (EGR1) in INS-1 beta-cells.

The catalytic subunit of gamma-glutamylcysteine ligase (GCLC) catalyses the rate-limiting step in the de novo synthesis of glutathione (GSH), which is involved in maintaining intracellular redox balance. GSH is especially important for antioxidant defense system since beta-cells show intrinsically low expression of antioxidant enzymes. In the present study, we investigated the regulatory mechanisms by which quercetin, a flavonoid, induces the expression of the GCLC gene in rat pancreatic beta-cell line INS-1.

Exendin-4 inhibits interleukin-1beta-induced iNOS expression at the protein level, but not at the transcriptional and posttranscriptional levels, in RINm5F beta-cells.

Cytokines such as interleukin-1beta (IL-1beta) stimulate inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction leading to beta-cell damage. Meanwhile, glucagon-like peptide-1 (GLP-1) and its potent analog exendin-4 (EX-4) were well known for beta-cell proliferation. However, the protective mechanisms of GLP-1 in beta-cells exposed to cytokines were not fully elucidated.

Exendin-4 induction of Egr-1 expression in INS-1 beta-cells: interaction of SRF, not YY1, with SRE site of rat Egr-1 promoter.

Glucagon-like peptide-1 (GLP-1) induces several immediate early response genes such as c-fos, c-jun, and early growth response-1 (Egr-1), which are involved in cell proliferation and differentiation. We recently reported that exendin-4 (EX-4), a potent GLP-1 agonist, upregulated Egr-1 expression via phosphorylation of CREB, a transcription factor in INS-1 beta-cells. This study was designed to investigate the role of another transcription factors, serum response factor (SRF) and Yin Yang-1 (YY1), in EX-4-induced Egr-1 expression.

Differential cholinergic modulation of Ca2+ transients evoked by backpropagating action potentials in apical and basal dendrites of cortical pyramidal neurons.

The effect of the cholinergic agonist carbachol (CCh) on backpropagating action potential (bAP)-evoked Ca2+ transients in distal apical and basal dendrites of layer 2/3 pyramidal neurons in the primary visual cortex of rats was studied using whole cell recordings and confocal Ca2+ imaging. In the presence of CCh (20 microM), initial bAP-evoked Ca2+ transients were followed by large propagating secondary Ca2+ transients that were restricted to proximal apical dendrites < or =40 microm from the soma. In middle apical dendrites (41-100 microm from the soma), Ca2+ transients evoked by AP bursts at 20 Hz, but not by single APs, were increased by CCh without secondary transients.

Effects of Apigenin on Glutamate-induced [Ca](i) Increases in Cultured Rat Hippocampal Neurons.

Flavonoids have been shown to affect calcium signaling in neurons. However, there are no reports on the effect of apigenin on glutamate-induced calcium signaling in neurons. We investigated whether apigenin affects glutamate-induced increase of free intracellular Ca(2+) concentration ([Ca(2+)](i)) in cultured rat hippocampal neurons, using fura-2-based digital calcium imaging and microfluorimetry.

CCAAT box is required for the induction of human thrombospondin-1 gene by trichostatin A.

Histone deacetylase (HDAC) inhibitors have been reported to inhibit angiogenesis as well as tumor growth. Thrombospondin-1 (TSP1) has been recognized as a potent inhibitor of angiogenesis. Such an action of TSP1 may account for the effect of HDAC inhibitors.

Effect of KAI1/CD82 on the beta1 integrin maturation in highly migratory carcinoma cells.

The KAI1/CD82 protein has been documented as the tumor metastasis suppressor in many types of human cancers. KAI1/CD82 regulates cell motility and invasiveness; however, the mechanism by which this occurs remains to be fully established. Several studies have shown that KAI1/CD82 modulates integrin-dependent signaling.

Open channel block of A-type, kv4.3, and delayed rectifier K+ channels, Kv1.3 and Kv3.1, by sibutramine.

The effects of sibutramine on voltage-gated K+ channel (Kv)4.3, Kv1.3, and Kv3.

Calcineurin-independent inhibition of KV1.3 by FK-506 (tacrolimus): a novel pharmacological property.

The interaction of FK-506 with K(V)1.3, stably expressed in Chinese hamster ovary cells, was investigated with the whole cell patch-clamp technique. FK-506 inhibited K(V)1.

Open channel block of Kv1.3 by rosiglitazone and troglitazone: Kv1.3 as the pharmacological target for rosiglitazone.

The effects of rosiglitazone and troglitazone were examined on cloned Kv1.3 channels stably expressed in Chinese hamster ovary cells using the whole-cell configuration of the patch-clamp technique. Rosiglitazone decreased the Kv1.

Proximal cyclic AMP response element is essential for exendin-4 induction of rat EGR-1 gene.

Glucagon-like peptide-1 and its potent agonist exendin-4 induce several immediate early response genes (IEGs) that code for transcription factors implicated in cell proliferation, differentiation, and apoptosis. We recently observed that early growth response factor-1 (EGR-1), an IEG product, was required for transcriptional activation of Ccnd1 (cyclin D1) gene by exendin-4. Herein, the regulatory mechanism whereby exendin-4 activates the transcription of EGR-1 gene was investigated in the pancreatic beta-cell line INS-1.

Desensitization of somatostatin-induced inhibition of low extracellular magnesium concentration-induced calcium spikes in cultured rat hippocampal neurons.

Neuronal excitability is inhibited by somatostatin, which might play important roles in seizure and neuroprotection. The possibility of whether the effect of somatostatin on neurotransmission is susceptible to desensitization was investigated. We tested the effects of prolonged exposure to somatostatin on 0.

Interaction of riluzole with the closed inactivated state of Kv4.3 channels.

The effect of riluzole on Kv4.3 was examined using the whole-cell patch-clamp technique. Riluzole inhibited the peak amplitude of Kv4.

Serotonin inhibits the induction of NMDA receptor-dependent long-term potentiation in the rat primary visual cortex.

An increase in serotonin [5-hydroxytryptamine (5-HT)] levels in the rat visual cortex is correlated with the developmental decrease in long-term potentiation (LTP), and 5-HT may play an important role in the closure of the critical period by regulating LTP. The effect of 5-HT on the induction of N-methyl-D-aspartate receptor (NMDAR)-dependent and metabotropic glutamate receptor (mGluR)-dependent LTP in visual cortex slices from young rats was investigated. The field potential in layer II/III was recorded by stimulating the underlying layer IV.

Spatial profile of back-propagating action potential-evoked Ca2+ transients in basal dendrites.

Calcium influx in basal dendrites evoked by back-propagating action potentials is important for understanding the input-specific modulation of synaptic transmission. Calcium transients evoked by back-propagating action potentials were measured for the basal dendrites of layer II/III pyramidal neurons in visual cortex slices. In contrast to apical dendrites, the peak calcium transients evoked by a single somatic action potential increased with distance from the soma.

Fluoxetine inhibits ATP-induced [Ca(2+)](i) increase in PC12 cells by inhibiting both extracellular Ca(2+) influx and Ca(2+) release from intracellular stores.

Fluoxetine, a widely used antidepressant, has additional effects, including the blocking of voltage-gated ion channels. We examined whether fluoxetine affects ATP-induced calcium signaling in PC12 cells using fura-2-based digital calcium imaging, an assay for [3H]-inositol phosphates (IPs) and whole-cell patch clamping. Treatment with ATP (100 microM) for 2 min induced increases in intracellular free Ca(2+) concentrations ([Ca(2+)](i)).

Inhibitory effects of epicatechin on interleukin-1beta-induced inducible nitric oxide synthase expression in RINm5F cells and rat pancreatic islets by down-regulation of NF-kappaB activation.

Cytokines that are released by infiltrating inflammatory cells around the pancreatic islets are involved in the pathogenesis of type 1 diabetes mellitus. Specifically, interleukin-1beta (IL-1beta) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, leading to the beta-cell damage. In activating this pathway, nuclear factor-kappaB (NF-kappaB) plays a crucial role, and many of the IL-1beta-sensitive genes contain NF-kappaB binding sites in their promoter regions.