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Toxoplasma gondii induce apoptosis of neural stem cells via endoplasmic reticulum stress pathway.

Toxoplasma gondii is a major cause of congenital brain disease; however, the underlying mechanism of neuropathogenesis in brain toxoplasmosi … nase (JNK) were activated in the NSCs co-cultured with the parasites. Pretreatment with endoplasmic reticulum stress (ERS) inhibitor (TUDCA) and caspase-12 inhibitor (Z-ATAD-FMK) inhibited the expression or activation of the key molecules involved in the ERS-mediated apoptotic pathway, and subsequently decreased the apoptosis levels of the NSCs induced by t …

Reduction of endoplasmic reticulum stress attenuates the defects caused by Drosophila mitofusin depletion.

Ablation of the mitochondrial fusion and endoplasmic reticulum (ER)-tethering protein Mfn2 causes ER stress, but whether this is just an epiphenomenon of mitochondrial dysfunction or a contributor to the phenotypes in mitofusin (Mfn)-depleted Drosophila melanogaster is unclear. In this paper, we show that reduction of ER dysfunction ameliorates the functional and developmental defects of flies lacking the single Mfn mitochondrial assembly regulatory factor (Marf). Ubiquitous or neuron- and muscle-specific Marf ablation was lethal, altering mitochondrial and ER morphology and triggering ER stre…

Disruption of sarcoendoplasmic reticulum calcium ATPase function in Drosophila leads to cardiac dysfunction.

Abnormal sarcoendoplasmic reticulum Calcium ATPase (SERCA) function has been associated with poor cardiac function in humans. While modifiers of SERCA function have been identified and studied using animal models, further investigation has been limited by the absence of a model system that is amenable to large-scale genetic screens. Drosophila melanogaster is an ideal model system for the investigation of SERCA function due to the significant homology to human SERCA and the availability of versatile genetic screening tools. To further the use of Drosophila as a model for examining the role of …

microRNA-199a-5p protects hepatocytes from bile acid-induced sustained endoplasmic reticulum stress.

Sustained endoplasmic reticulum (ER) stress has been linked to cell death and the pathogenesis of many liver diseases, including toxic liver, cholestasis, and infectious liver disease. The cellular pathways that attenuate hepatic ER stress have been the focus of many recent studies, but the role of microRNAs (miRNA) in this process remains unknown. Here, we report that one of the most abundant miRNAs in hepatocytes, miR-199a-5p, was elevated in both bile acid- and thapsigargin (TG)-stimulated cultured hepatocytes, as well as in the liver of bile duct-ligated mice. We identify the misfolded pro…

Nongenomic STAT5-dependent effects on Golgi apparatus and endoplasmic reticulum structure and function.

We report unexpected nongenomic functions of signal transducer and activator of transcription (STAT) 5 species in the cytoplasm aimed at preserving the structure and function of the Golgi apparatus and rough endoplasmic reticulum (ER) in vascular cells. Immunoimaging and green fluorescent protein-tagged-STAT5a protein localization studies showed the constitutive association of nonphosphorylated STAT5a, and to a lesser extent STAT5b, with the Golgi apparatus and of STAT5a with centrosomes in human pulmonary arterial endothelial and smooth muscle cells. Acute knockdown of STAT5a/b species using …

Sulfur dioxide inhibits excessively activated endoplasmic reticulum stress in rats with myocardial injury.

It has been demonstrated that excessively activated endoplasmic reticulum stress (ERS) is related to myocardial injury. The study was designed to explore the possible role of sulfur dioxide (SO(2)) in protecting excessively activated ERS in rats with isoproterenol (ISO)-induced myocardial injury. Wistar rats were randomly divided into control, ISO, and ISO + SO(2) groups. Cardiac catheterization-derived hemodynamic parameters and myocardial enzymes in plasma were measured. Microstructure changes in myocardial tissues were examined. Cardiomyocyte apoptosis was detected by TUNEL method. Myocardi…

Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress.

Familial neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene locus of arginine vasopressin (AVP), an antidiuretic … RNA poly(A) tail length in the FNDI mice, a case in which aggregates accumulated in the endoplasmic reticulum (ER) of the hypothalamic AVP neurons. Expression levels of AVP heteronuclear RNA in the supraoptic nucleus, a sensitive indicator for gene transcription, were not significantly different between FNDI and wild-type mice. Incubation of hypothalamic ex …

Endoplasmic reticulum stress in maternal diabetes-induced cardiac malformations during critical cardiogenesis period.

BACKGROUND: Cardiac abnormalities, including atrioventricular (AV) septal defects (AVSDs), are the most common birth defects in diabetic embryopathy. The AV septum is derived from the endocardial cushions, which undergo development and remodeling during septation. The impact of maternal diabetes on these processes needs to be identified. Maternal diabetes disturbs the function of the endoplasmic reticulum (ER). The role of ER stress in cardiac malformation remains to be delineated to gain information for developing therapy. METHODS: Female mice were induced diabetic via intravenous injection …

Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress.

Prion-related disorders (PrDs) are fatal neurodegenerative disorders characterized by progressive neuronal impairment as well as the accumulation of an abnormally folded and protease resistant form of the cellular prion protein, termed PrP(RES). Altered endoplasmic reticulum (ER) homeostasis is associated with the occurrence of neurodegeneration in sporadic, infectious and familial forms of PrDs. The ER operates as a major intracellular calcium store, playing a crucial role in pathological events related to neuronal dysfunction and death. Here we investigated the possible impact of PrP misfold…

Поток кальция между эндоплазмическим ретикулумом и митохондрионом способствует апоптозу, вызванному полиомиелитвирусом.

Мы показываем, что полиомиелитвирусная инфекция (PV) вызывает увеличение концентрации цитосолического кальция (Ca(2+)) в нейробластомных клетках IMR5, по крайней мере частично через Ca(2+) высвобождение из эндоплазмического ретикулума люмена через каналы иноситола 1,4,5-трифосфатного рецептора (IP(3)R) и рианодина рецептора (RyR). Это приводит к аккумулированию Ca(2+) в митохондрии через митохондриальный канал Ca(2+) и анионный канал, зависящий от напряжения (VDAC). Это увеличение концентрации митохондриала Ca(2+) в PV-зараженных клетках ведет к митохондриальной дисфункции и апоптозу.

Совпадение в аннотации оригинала
We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca(2+)) concentration in neuroblastoma IMR5 cells, at least partly through Ca(2+) release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP(3)R) and ryanodine receptor (RyR) channels. This leads to Ca(2+) accumulation in mitochondria through t…

The cardiac sarcoplasmic/endoplasmic reticulum calcium ATPase: a potent target for cardiovascular diseases.

The cardiac isoform of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a) is a calcium ion (Ca(2+)) pump powered by ATP hydrolysis. SERCA2a transfers Ca(2+) from the cytosol of the cardiomyocyte to the lumen of the sarcoplasmic reticulum during muscle relaxation. As such, this transporter has a key role in cardiomyocyte Ca(2+) regulation. In both experimental models and human heart failure, SERCA2a expression is significantly decreased, which leads to abnormal Ca(2+) handling and a deficient contractile state. Following a long line of investigations in isolated cardiac myocytes an…

Endoplasmic reticulum chaperone protein GRP-78 mediates endocytosis of dentin matrix protein 1.

Dentin matrix protein 1 (DMP1), a phosphorylated protein present in the mineral phase of both vertebrates and invertebrates, is a key regulatory protein during biogenic formation of mineral deposits. Previously we showed that DMP1 is localized in the nuclear compartment of preosteoblasts and preodontoblasts. In the nucleus DMP1 might play an important role in the regulation of genes that control osteoblast or odontoblast differentiation. Here, we show that cellular uptake of DMP1 occurs through endocytosis. Interestingly, this process is initiated by DMP1 binding to the glucose-regulated prote

Impact of the endoplasmic reticulum stress response in spinal cord after transient ischemia.

BACKGROUND: Delayed paraplegia after operation of the thoracic aorta is considered to be related to vulnerability of motor neurons to ischemia. Recently, endoplasmic reticulum (ER) stress has been reported to participate in neuronal cell death. In the present study, we investigate the expression of ER stress-related molecules and discuss the relationship between neuronal vulnerability and ER stress after transient ischemia in the spinal cord. METHODS: A rabbit spinal cord ischemia model was generated using a balloon catheter. In this model, spinal motor neurons show selectively delayed neuron…

Endoplasmic reticulum stress is involved in arsenite-induced oxidative injury in rat brain.

The mechanism underlying sodium arsenite (arsenite)-induced neurotoxicity was investigated in rat brain. Arsenite was locally infused in the … e-induced apoptosis was mediated via two different organelle pathways, mitochondria and endoplasmic reticulum (ER). For mitochondrial activation, cytosolic cytochrome c and caspase-3 levels were elevated in the arsenite-infused SN. In ER pathway, arsenite increased activating transcription factor-4, X-box binding protein 1, C/EBP homologues protein (CHOP) a …

Nitroxyl improves cellular heart function by directly enhancing cardiac sarcoplasmic reticulum Ca2+ cycling.

Heart failure remains a leading cause of morbidity and mortality worldwide. Although depressed pump function is common, development of effec … wn. Here, we show that this activity results from a direct interaction of HNO with the sarcoplasmic reticulum Ca(2+) pump and the ryanodine receptor 2, leading to increased Ca(2+) uptake and release from the sarcoplasmic reticulum. HNO increases the open probability of isolated ryanodine-sensitive Ca(2+)-release channels and accelerates Ca(2+) reuptake into …

Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice.

BACKGROUND & AIMS: Alcohol-induced hyperhomocysteinemia has been reported in rats and humans. Hyperhomocysteinemia has been associated with endoplasmic reticulum (ER) stress leading to the activation of ER-dependent apoptosis or up-regulation of lipid synthesis. This novel ER stress mechanism of alcoholic liver injury was studied in the model of intragastric alcohol-fed mice. METHODS: Effects of alcohol on gene expression were analyzed using cDNA microarrays, RT-PCR, and Western blots over a period of 6 weeks. Liver injury was examined by histologic staining and TUNEL. RESULTS: We observed f…

Inhibition of skeletal sarcoplasmic reticulum Ca2+-ATPase activity by deferoxamine nitroxide free radical.

Deferoxamine is an inhibitor of iron-dependent free radical reactions. Despite the antioxidant roles, prolonged clinical use of the chelator … peroxidase in the presence of H2O2 are capable of inactivating Ca2+-ATPase of skeletal sarcoplasmic reticulum microsomes as a model system with which to explore the effect of the radical on a biological membrane. Ca2+-ATPase activity of sarcoplasmic reticulum was depressed by exposure to Fenton's reagent (H2O2/FeSO4); the observed effect was significantly e …

Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153).

The gene encoding C/EBP-homologous protein (CHOP), also known as growth arrest and DNA-damage-inducible gene 153 (GADD153), is activated by agents that adversely affect the function of the endoplasmic reticulum (ER). Because of the pleiotropic effects of such agents on other cellular processes, the role of ER stress in inducing CHOP gene expression has remained unclear. We find that cells with conditional (temperature-sensitive) defects in protein glycosylation (CHO K12 and BHK tsBN7) induce CHOP when cultured at the nonpermissive temperature. In addition, cells that are defective in initiatin…

Endoplasmic reticulum-to-cytosol transport of free polymannose oligosaccharides in permeabilized HepG2 cells.

Free polymannose oligosaccharides have recently been localized to both the vesicular and cytosolic compartments of HepG2 cells. Here we investigated the possibility that free oligosaccharides originating in the lumen of the endoplasmic reticulum (ER) are transported directly into the cystosol. Incubation of permeabilized cells in the absence of ATP at 37 degrees C led to the intravesicular accumulation of free Man9GlcNAc2 which was generated from dolichol-linked oligosaccharide in the ER. This oligosaccharide remained stable within the permeabilized cells unless ATP was added to the incubation…

Porcine malignant hyperthermia susceptibility: increased calcium-sequestering activity of skeletal muscle sarcoplasmic reticulum.

This study tested the hypothesis that calcium-sequestration by isolated sarcoplasmic reticulum was abnormal in skeletal muscle of malignant hyperthermia-susceptible swine. A heavy sarcoplasmic reticulum fraction was isolated from malignant hyperthermia and control muscle using differential and density-gradient centrifugation. Prior to onset of malignant hyperthermia, calcium-sequestering activity (Vmax at 37 degrees C, mumol calcium/mg/min) was twofold increased in malignant hyperthermia sarcoplasmic reticulum compared to control sarcoplasmic reticulum (1.96 +/- 0.50 versus 4.00 +/- 0.87, P le…