Protective effects of calcium ions via L-type calcium channels and NMDA receptors on prostaglandin E-induced apoptosis in rat cortical cells.

Calcium ions mediate a variety of physiological responses of developing neurons including survival. The purpose of this study was to examine the effect of calcium influx through L-type calcium channels (LTCCs) or NMDA receptors on prostaglandin E (PGE)-induced apoptosis in rat cortical cells. Cultures of rat cortical cells were prepared from an embryonic day 18 rat neocortex.

Anti-inflammatory effects of lipoic acid through inhibition of GSK-3β in lipopolysaccharide-induced BV-2 microglial cells.

Activated microglial cells play an important role in immune and inflammatory responses in CNS and play a role in neurodegenerative diseases. We examined the effects of lipoic acid (LA) on inflammatory responses of BV-2 microglial cells activated by lipopolysaccharide (LPS), and explored the underlying mechanisms of action of LA. BV-2 cells treated with LPS showed an up-regulation of mRNA of the pro-inflammatory molecules, inducible nitric oxide synthase (iNOS).

Protective action of nipradilol mediated through S-nitrosylation of Keap1 and HO-1 induction in retinal ganglion cells.

Nipradilol (Nip), which has α1- and β-adrenoceptor antagonist and nitric oxide (NO)-donating properties, has clinically been used as an anti-glaucomatous agent in Japan. NO mediates cellular signaling pathways that regulate physiological functions. The major signaling mechanisms mediated by NO are cGMP-dependent signaling and protein S-nitrosylation-dependent signalings.

Apoptosis induced by SRC-family tyrosine kinase inhibitors in cultured rat cortical cells.

In the central nervous system, members of the Src family of tyrosine kinases (SFKs) are widely expressed and are abundant in neurons. The purpose of this study is to examine whether glycogen synthase-3 (GSK-3) is involved in SFK inhibitor-induced apoptosis. PP2 and SU6656, SFK inhibitors, increased apoptotic cell death with morphological changes that were characterized by cell shrinkage, chromatin condensation, or nuclear fragmentation.

5-S-GAD attenuates Fe²+-induced lipid peroxidation and cell death in a neuronal cell model.

Iron accumulation in brain is associated with a number of common neurodegenerative disorders. N-β-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), a novel catechol derivative, was isolated from adult flesh fly as a defense substance. We examined the effect of 5-S-GAD on Fe²+-induced lipid peroxidation and cell death in PC12 cells.

Colchicine-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells.

The purpose of this study was to examine whether glycogen synthase kinase-3 (GSK-3) is involved in colchicine-induced cell death in PC12 cells by using GSK inhibitors. Colchicine increased apoptotic cell death with morphological changes characterized by cell shrinkage and nuclear condensation or fragmentation. GSK-3 inhibitors such as alsterpaullone, SB216763, and AR-A014418 prevented colchicine-induced cell death and caspase-3 activation.

Chelation of extracellular calcium-induced cell death was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells.

Calcium ion is a secondary messenger that mediates a variety of physiological responses of neurons, including cell survival responses. To determine the role of calcium in regulating neuronal survival and death, we examined whether chelation of extracellular calcium with EGTA induces caspase-dependent apoptotic cell death and whether glycogen synthase kinase-3 is involved in EGTA-induced cell death in PC12 cells. EGTA increased apoptotic cell death with morphological changes characterized by cell shrinkage and nuclear condensation and fragmentation accompanied by caspase activation.

Microbulbifer variabilis sp. nov. and Microbulbifer epialgicus sp. nov., isolated from Pacific marine algae, possess a rod-coccus cell cycle in association with the growth phase.

Phylogenetic and taxonomic characterization was performed for 14 strains of bacteria that produce anticancer antibiotics (pelagiomicins) (represented by strain Ni-2088(T)) and one strain that produces UV-absorbing substances (strain F-104(T)), isolated from marine algae and seagrass collected from coastal areas of tropical Pacific islands and a subtropical island of Japan. All 15 isolates were Gram-negative, strictly aerobic, non-motile and non-spore-forming. Sequence analysis of the 16S rRNA gene showed that the isolates occupied positions in the phylogenetic radiation of the genus Microbulbifer, with similarities of 93.

Benzyl alcohol inhibits N-methyl-D: -aspartate receptor-mediated neurotoxicity and calcium accumulation in cultured rat cortical neurons.

The purpose of this study is to examine whether benzyl alcohol affects N-methyl-D-aspartate (NMDA) receptor in cortical cells. Benzyl alcohol (0.5-2 mM) inhibited NMDA-induced cytotoxicity.

Calmodulin inhibitor-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells.

Calmodulin is known to transduce Ca(2+) signals by interacting with specific target proteins. In order to determine the role of calmodulin in regulating neuronal survival and death, we examined, whether calmodulin inhibitors induce caspase-dependent apoptotic cell death, and whether glycogen synthase kinase-3 is involved in calmodulin inhibitor-induced cell death in PC12 cells. W13, a calmodulin specific inhibitor increased apoptotic cell death with morphological changes characterized by cell shrinkage and nuclear condensation of fragmentation.

Temperature-dependent N-methyl-D-aspartate receptor-mediated cytotoxicity in cultured rat cortical neurons.

Hypothermia protects against hypoxic or ischemic damage. However, the mechanisms by which brain cooling prevents hypoxic or ischemic damage are not clear. We examined whether hypothermia protects against excitotoxicity in cultured cortical cells.

Caspase-dependent apoptosis induced by thapsigargin was prevented by glycogen synthase kinase-3 inhibitors in cultured rat cortical neurons.

Calcium ion is essential for cellular functions including signal transduction. Uncontrolled calcium stress has been linked causally to a variety of neurodegenerative diseases. Thapsigargin, which inhibits Ca(2+)-ATPase in the endoplasmic reticulum (ER) and blocks the sequestration of calcium by the ER, induced apoptotic cell death (chromatin condensation and nuclear fragmentation) accompanied by GRP78 protein expression and caspase-3 activation in rat fetal cortical neurons (days in vitro 9-10).

Cyclosporine A- and FK506-induced apoptosis in PC12 cells.

The purpose of this study was to examine, using glycogen synthase kinase (GSK) inhibitors, whether GSK-3 is involved in cyclosporine A (CsA)- and FK506-induced apoptosis in PC12 cells. CsA and FK506 increased apoptotic cell death with morphological changes characterized by cell shrinkage and nuclear condensation or fragmentation. Nerve growth factor (NGF) completely blocked cell death.

Caspase-dependent apoptosis induced by calcineurin inhibitors was prevented by glycogen synthase kinase-3 inhibitors in cultured rat cortical cells.

Calcineurin is selectively enriched within neurons of the central nervous system. The mechanism of calcineurin inhibitor-induced neurotoxicity remains poorly understood. The purpose of this study is to examine whether glycogen synthase-3 (GSK-3) is involved in calcineurin inhibitor-induced apoptosis.

Thapsigargin-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells.

Uncontrolled calcium stress has been linked causally to a variety of neurodegenerative diseases, including ischemia, excitotoxicity and Alzheimer's disease. Thapsigargin, which increases [Ca2+]i, induces apoptotic cell death (chromatin condensation and DNA fragmentation) accompanied by caspase-3 activation in PC12 cells. We examined whether GSK-3 is involved in thapsigargin-induced cell death by using GSK-3 inhibitors in PC12 cells.

Prevention of rat cortical neurons from prostaglandin E2-induced apoptosis by glycogen synthase kinase-3 inhibitors.

Cyclooxygenase-2 (COX-2) induction and prostaglandin E(2) (PGE(2)) elevation have been reported to occur after cerebral ischemic insult. PGE(2) induces apoptosis through the PGE(2) EP2 receptor by a cAMP-dependent pathway. Glycogen synthase kinase-3 (GSK-3) affects many fundamental cellular functions.

Prostaglandin E2 deteriorates N-methyl-D-aspartate receptor-mediated cytotoxicity possibly by activating EP2 receptors in cultured cortical neurons.

The activation of glutamate receptors, particularly N-methyl-D-aspartate (NMDA) receptors, initiates ischemic cascade in the early stages of cerebral ischemia. Postischemia, cerebral ischemia is also associated with an inflammatory reaction that contributes to tissue damage. The up-regulation of neuronal cyclooxygenase-2 (COX-2) and elevation of prostaglandin E2 (PGE2) have been reported to occur after cerebral ischemic insult.

Ketamine-induced apoptosis in cultured rat cortical neurons.

Recent data suggest that anesthetic drugs cause neurodegeneration during development. Ketamine is frequently used in infants and toddlers for elective surgeries. The purpose of this study is to determine whether glycogen synthase kinase-3 (GSK-3) is involved in ketamine-induced apoptosis.

Glutathione depletion promotes aluminum-mediated cell death of PC12 cells.

Exposure of rat phenochromocytoma cells (PC12 cells) to aluminum maltolate complex, Al(maltol)3, induced a decrease in intracellular glutathione (GSH) concentration, resulting in a facilitated release of lactate dehydrogenase (LDH) from the cell and an increase in trypan blue-stained cells. Similar phenomena were observed as the cells were treated with L-buthione-[S,R]-sulfoximine (BSO) in the presence of Al(maltol)3. On the other hand, treatment of PC 12 cells with BSO alone in the absence of Al(maltol)3 did not affect the cell viability.

Glycogen synthase kinase-3 inhibitors prevent caspase-dependent apoptosis induced by ethanol in cultured rat cortical neurons.

The effect of ethanol on cell viability was examined in rat cultured cortical neurons. Ethanol induced apoptosis, which was characterized by cell shrinkage, nuclear condensation or fragmentation and internucleosomal DNA fragmentation. Ethanol-induced apoptosis was prevented by N-methyl-d-aspartate (NMDA), an agonist of the NMDA receptor, which is a subtype of ionotropic glutamate receptors.

NMDA receptor 2B-selective antagonist ifenprodil-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in cultured rat cortical neurons.

The N-methyl-d-aspartate (NMDA) receptor 2B-selective antagonist ifenprodil induced morphological changes which were characterized by cell shrinkage, nuclear condensation or fragmentation, and internucleosomal DNA fragmentation in rat cultured cortical cells. Ifenprodil increased the apoptotic cell death in a dose-dependent manner (0.5-10 microM).

Prostaglandin E2 induced caspase-dependent apoptosis possibly through activation of EP2 receptors in cultured hippocampal neurons.

Cyclooxygenase-2 (COX-2) induction and prostaglandin E2 elevation have been reported to occur after cerebral ischemic insult. To evaluate whether the cyclooxygenase-2 reaction product prostaglandin E2 is directly related to induction of apoptosis in neuronal cells, the effect of prostaglandin E2 on cell viability was examined in hippocampal cells. Prostaglandin E2 (5-25 microM) induced apoptosis in a dose-dependent manner 48 h after addition to the cells, which was characterized by cell shrinkage, nuclear condensation or fragmentation and attenuated by a protein synthesis inhibitor, cycloheximide.

Nerve growth factor protects against aluminum-mediated cell death.

In the present study, we examined the effect of two salts of aluminum (Al), aluminum maltolate (Almal) and aluminum chloride (AlCl(3)), on the cell viability of PC12 cells in the absence and presence of nerve growth factor (NGF). A 72-h exposure of PC12 cells to Almal (300 microM) resulted in a marked increase of lactic dehydrogenase (LDH) release from the cells and a decrease of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) activity. These results indicate that Almal induces a decrease in the cell viability.

Prostaglandin E(2) induces caspase-dependent apoptosis in rat cortical cells.

Up-regulation of neuronal cyclooxygenase-2 (COX-2) and the elevation in prostaglandin E(2) (PGE(2)) have been reported to occur after cerebral ischemic insult. To evaluate whether the COX-2 reaction product PGE(2) is directly related to induction of apoptosis in neuronal cells, the effect of PGE(2) on cell viability was examined in rat cortical cells. PGE(2) induced apoptosis in a dose-dependent manner (5-25 microM) 48 h after addition to the cells, which was characterized by cell shrinkage, nuclear condensation or fragmentation, and internucleosomal DNA fragmentation.