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Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.

OBJECTIVE: Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recentl … ls decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by inhibiting binding of NF- κB to their promoter regions and blocked attachme …

N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) promote growth and inhibit differentiation of glioma stem-like cells.

Metabolic reprogramming is a pathological feature of cancer and a driver of tumor cell transformation. N-Acetylaspartate (NAA) is one of the … differentiation of Oli-Neu cells and proneural GSCs. Interestingly, ASPA was expressed in both the cytosol and nuclei of GSCs and exhibited greatest nuclear immunoreactivity in differentiation-resistant GSCs. Both NAA and NAAG elicited the expression of a novel immunoreactive ASPA species in select GSC nuclei, suggesting differential ASPA regulation in r …

Glucotoxic conditions induce endoplasmic reticulum stress to cause caspase 3 mediated lamin B degradation in pancreatic β-cells: protection by nifedipine.

Nuclear lamins form the lamina on the interior of the nuclear envelope, and are involved in the regulation of various cellular processes, in … B leading to accumulation of the degraded products in non-relevant cellular compartments, including cytosol. Moreover, the effects of high glucose on caspase 3 activation and lamin B degradation were mimicked by thapsigargin, a known inducer of endoplasmic reticulum stress (ER stress). Nifedipine, a known blocker of calcium channel activation, inhibited h …

SHOX triggers the lysosomal pathway of apoptosis via oxidative stress.

The SHOX gene encodes for a transcription factor important for normal bone development. Mutations in the gene are associated with idiopathic … stress that, in turn, induces lysosomal membrane rupture with release of active cathepsin B to the cytosol and subsequent activation of the intrinsic apoptotic pathway characterized by mitochondrial membrane permeabilization and caspase activation. Importantly, cells expressing SHOX R153L or L185X did not display any of these features. Given the fact tha …

Acute effects of rotavirus and malnutrition on intestinal barrier function in neonatal piglets.

AIM: To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model. … ion of the tight junction protein, occludin, in the cell membrane and increased localization in the cytosol. CONCLUSION: Overall, malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.

Coxiella burnetii exploits host cAMP-dependent protein kinase signalling to promote macrophage survival.

Intracellular bacterial pathogens often subvert apoptosis signalling to regulate survival of their host cell, allowing propagation of the bacterial population. Coxiella burnetii, the intracellular agent of human Q fever, inhibits host cell apoptosis through several mechanisms, including prevention of mitochondrial cytochrome c release, triggering of an anti-apoptotic transcriptional programme, and activation of pro-survival kinases. To control host cell survival, C. burnetii delivers effector proteins to the eukaryotic cytosol using a specialized Dot/Icm type IV secretion system (T4SS). Effect…

Протеиновый белок " Coxiella signetii " разрушает клатриновый везикулярный оборот патогенных вакуол биогенеза.

Успешная колонизация макрофага с помощью Coxiella signetii, которая является причиной лихорадки Q человека, требует биогенеза, ориентированного на патоген, большого паразитообразного паразита (PV) с фаголизомными характеристиками. В то же время, согласно прогнозам, для сбора мембранных белков, поставляемых цитозолу в результате дефектного оборота органелл/внутреннего умножения (Dot/Icm) типа 4B, требуются белки-эффекторы. Здесь мы описываем участие клатринового везикулярного оборота в производстве PV и участие этого пути системой C. signetii типа 4B подстрата Coxiella vacuolar белка A (CvpA).

Совпадение в аннотации оригинала
Successful macrophage colonization by Coxiella burnetii, the cause of human Q fever, requires pathogen-directed biogenesis of a large, growt … PV development are poorly defined; however, it is predicted that effector proteins delivered to the cytosol by a defective in organelle trafficking/intracellular multiplication (Dot/Icm) type 4B secretion system are required for membrane recruitment. Here, we describe involvement of clathrin-mediated vesicular trafficking in PV generation and the engageme …

A differential fluorescence-based genetic screen identifies Listeria monocytogenes determinants required for intracellular replication.

Listeria monocytogenes is a Gram-positive, facultative intracellular pathogen capable of causing severe invasive disease with high mortality rates in humans. While previous studies have largely elucidated the bacterial and host cell mechanisms necessary for invasion, vacuolar escape, and subsequent cell-to-cell spread, the L. monocytogenes factors required for rapid replication within the restrictive environment of the host cell cytosol are poorly understood. In this report, we describe a differential fluorescence-based genetic screen utilizing fluorescence-activated cell sorting (FACS) and hi…

Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene.

N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NA-DCVC) has been detected in the urine of humans exposed to trichloroethylene and its related su … active with GSH. Because NA-DCVCS exhibited a longer half-life than DCVCS and addition of rat liver cytosol enhanced GSH conjugate formation, catalysis of GSH conjugate formation by the liver could explain the lower toxicity of NA-DCVCS in comparison with DCVCS. Collectively, these results provide clear evidence that NA-DCVCS formation could play a signif …

Antiviral activity of salivary microRNAs for ophthalmic herpes zoster.

Ophthalmic herpes zoster is a common ocular infection caused by the varicella-zoster virus (VZV). Viral mRNA transcripts play a major role i … icrovesicles seem to enter into the corneal cells through the clathrin-mediated endocytosis. In the cytosol, human salivary miRNAs base-pair with specific viral mRNAs and inhibit their translation, thus limiting the replication of the virus.

Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein.

Innate sensing of microbial components is well documented to occur at many cellular sites, including at the cell surface, in the cytosol, and in intracellular vesicles, but there is limited evidence of nuclear innate signaling. In this study we have defined the mechanisms of interferon regulatory factor-3 (IRF-3) signaling in primary human foreskin fibroblasts (HFF) infected with herpes simplex virus 1 (HSV-1) in the absence of viral gene expression. We found that the interferon inducible protein 16 (IFI16) DNA sensor, which is required for induction of IRF-3 signaling in these cells, is nucle…

Inhibitory effects of Scutellaria baicalensis extract on hepatic stellate cells through inducing G2/M cell cycle arrest and activating ERK-dependent apoptosis via Bax and caspase pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The bioactive components extracted from Scutellaria baicalensis Georgi (SB) have been widely used for anti-c … vated caspase-3, poly-(ADP-ribose) polymerase (PARP) cleavage, and release of cytochrome c into the cytosol in a time-dependent manner. A 24h treatment of SBEE induced G(2)/M cell cycle arrest with increased expression of p21 and downregulation of cdc2 and cyclin B1 protein levels. Again, SBEE induced bax expression with concomitant decrease of bcl-2 and …

Mitochondrial Dysfunction during Brain Aging: Role of Oxidative Stress and Modulation by Antioxidant Supplementation.

Mitochondrial dysfunction and oxidative stress are two interdependent and reinforcing damage mechanisms that play a central role in brain ag … e can initiate mitochondrial biogenesis program and activate various transcriptional factors in the cytosol to boost up the antioxidative capacity of the mitochondria and the cell. However, a high level of oxidative stress finally inflicts critical damage to the oxidative phosphorylation machinery and mitochondrial DNA (mtDNA). The latter part of the arti …

Reactive oxygen species removal activity of davallialactone reduces lipopolysaccharide-induced pulpal inflammation through inhibition of the extracellular signal-regulated kinase 1/2 and nuclear factor kappa b pathway.

INTRODUCTION: Davallialactone, hispidin analogues derived from the mushroom Inonotus xeranticus, has antioxidant properties. This study exam … cells through the suppression of ERK1/2 activation followed by blockage of NF-κB translocation from cytosol into nuclear. Therefore, the good anti-inflammatory capacity of davallialactone might be used for oral diseases such as pulpitis and periodontitis.

Antidepressants elevate GDNF expression and release from C₆ glioma cells in a β-arrestin1-dependent, CREB interactive pathway.

Glial cell line-derived neurotrophic factor (GDNF), essential for neuronal survival, plasticity and development, has been implicated in the … cid) or to the antipsychotic haloperidol. Only ADs significantly elevated β-arrestin1 levels in the cytosol, while reducing phospho-β-arrestin1 levels in the cell nuclear fraction. ADs significantly increased both GDNF expression and release from the cells, but were unable to induce such effects in β-arrestin1 knock-down cells. Chronic AD treatment signif …

Differential DNA damage responses in p53 proficient and deficient cells: cisplatin-induced nuclear import of XPA is independent of ATR checkpoint in p53-deficient lung cancer cells.

Nucleotide excision repair (NER) and ataxia telangiectasia mutated (ATM)/ATR (ATM- and RAD3-related) DNA damage checkpoints are among the major pathways that affect the chemotherapeutic efficiency of the anticancer drug cisplatin. Xeroderma pigmentosum group A (XPA) protein plays a crucial role in NER including both global genome repair (GG-NER) and transcription-coupled repair (TC-NER) subpathways, and has been a potential target for improving cisplatin therapeutic effects. We report here that XPA translocates from the cytosol into the nucleus after DNA damage induced by UV irradiation and ci…

Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency.

The purinosome is a multienzyme complex composed by the enzymes active in de novo purine synthesis (DNPS) that cells transiently assemble in their cytosol upon depletion or increased demand of purines. The process of purinosome formation has thus far been demonstrated and studied only in human epithelial cervical cancer cells (HeLa) and human liver carcinoma cells (C3A) transiently expressing recombinant fluorescently labeled DNPS proteins. Using parallel immunolabeling of various DNPS enzymes and confocal fluorescent microscopy, we proved purinosome assembly in HeLa, human hepatocellular live…

Glucose-6-phosphate isomerase deficiency results in mTOR activation, failed translocation of lipin 1α to the nucleus and hypersensitivity to glucose: Implications for the inherited glycolytic disease.

Inherited glucose-6-phosphate isomerase (GPI) deficiency is the second most frequent glycolytic erythroenzymopathy in humans. Patients prese … ther glucose-derived metabolites, leading to activation of mTOR and sequestration of lipin 1 to the cytosol, preventing its proper functioning. These results shed light on the mechanism underlying the pathologies associated with inherited GPI deficiency and the variability in the severity of the symptoms observed in these patients.

Pathways for ATP release by bovine ciliary epithelial cells, the initial step in purinergic regulation of aqueous humor inflow.

ATP release by nonpigmented (NPE) and pigmented (PE) ciliary epithelial cells is the enabling step in purinergic regulation of aqueous humor … (7)) antagonist KN-62. Bafilomycin A1 acts by reducing the driving force for uptake of ATP from the cytosol into vesicles. The reducing agent dithiothreitol reduced probenecid-blockable ATP release. Similar results were obtained with NPE and PE cell lines. Pannexins PX1-3, connexins Cx43 and Cx40, and P2RX(7) were identified in native cells and cell lines …

Preclinical evidence for a beneficial impact of valproate on the response of small cell lung cancer to first-line chemotherapy.

Prognosis of small cell lung carcinoma (SCLC) is particularly poor, less than 5% of patients with extensive stage being alive after two year … tochondria and cleaved in an 18kDa isoform. Cytochrome c is released from the mitochondria into the cytosol. Transcriptomic analyses by microarray show that VPA modulates transcription of genes (Na(+)/K(+) ATPase, Bcl-xL) involved in chemoresistance to cisplatin and etoposide. Finally, the efficacy of VPA combined with cisplatin and etoposide is supported …