Zhenqi Granules Attenuates the Inflammatory Response of Pulmonary Epithelial Cells by Inhibiting Endoplasmic Reticulum Stress in MRSA Infection
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PROVIDER: PRJNA1113538 | ENA |
REPOSITORIES: ENA
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Project description:The severe inflammatory response of pulmonary epithelial cells is the main pathological feature of pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Zhenqi granules (ZQ), a compound herbal formula composed of Astragalus membranaceus and Ligustrum lucidum, has potential therapeutic effects on this inflammatory response, but its mechanism of action is still unclear. The study aims to explore the effect and mechanism of ZQ on the inflammatory response induced by establishing an in vitro model of MRSA-infected human pulmonary bronchial epithelial cells (MRSA-BEAS-2B). ZQ (10 mg/mL) had no inhibitory effect on MRSA or its biofilm, but it reduced the levels of LDH and c-di-AMP in MRSA-BEAS-2B cells. The mechanism is attributed to the downregulation of endoplasmic reticulum-related protein pathways, specifically involving a decrease in endoplasmic reticulum stress-related proteins such as STING and ERAdP; a decrease in inflammation pathway-related factors such as NF-ĸB, IFR3, NLRP3, and TLR4; and an increase in the STING antagonist RECON. These effects resulted in a reduction in the proinflammatory cytokines IFN-β, IL-1β, IL-6, and IL-18, thereby inhibiting pulmonary inflammation. ZQ attenuates the inflammatory response of pulmonary epithelial cells by inhibiting c-di-AMP-related endoplasmic reticulum stress during MRSA infection. This study provides a basis for the clinical application of ZQ and improves the development of treatment strategies for pulmonary MRSA infection.
2024-10-19 | GSE267856 | GEO
Project description:In eukaryotic cells, the spatial regulation of protein expression is frequently conferred through the coupling of mRNA localization and the local control of translation. mRNA localization to the endoplasmic reticulum (ER) is a prominent example of such regulation and serves a ubiquitous role in segregating the synthesis of secretory and integral membrane proteins to the ER. Recent genomic and biochemical studies have now expanded this view to suggest a role for the ER in global protein synthesis. We have utilized cell fractionation and ribosome profiling to obtain a genomic survey of the subcellular organization of mRNA translation and report that ribosomal loading of mRNAs, a proxy for mRNA translation, is biased to the ER. Notably, ER-associated mRNAs encoding both cytosolic and topogenic signal-encoding proteins display similar ribosome loading densities, suggesting that ER-associated ribosomes serve a global role in mRNA translation. We propose that the partitioning of mRNAs and their translation between the cytosol and ER compartments may represent a novel mechanism for the post-transcriptional regulation of gene expression. HEK293 cells were fractionated between the cytosol and endoplasmic reticulum. Within each fraction, ribosome footprints were generated and sequenced. In parallel, total mRNA was sequenced.
2011-12-20 | E-GEOD-31539 | biostudies-arrayexpress
Project description:Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.
2023-11-26 | GSE232677 | GEO
Project description:Tunicamycin-induced Endoplasmic Reticulum-Quality Control Pathway and Endoplasmic Reticulum-Associated Degradation Mechanism in the diatom Phaeodactylum tricornutum
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Project description:EMD37 triggers endoplasmic reticulum stress in cancer cells
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Project description:In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments. Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40) and homologous yeast guided entry of tail-anchored proteins (GET) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay. We set out to uncover additional targeting proteins using unbiased high-content screening approaches. To this end, we performed a systematic visual screen using the yeast Saccharomyces cerevisiae, and uncovered three uncharacterized proteins whose loss affected targeting. We suggest that these proteins work together and demonstrate that they function in parallel with SRP and GET to target a broad range of substrates to the endoplasmic reticulum. The three proteins, which we name Snd1, Snd2 and Snd3 (for SRP-independent targeting), can synthetically compensate for the loss of both the SRP and GET pathways, and act as a backup targeting system. This explains why it has previously been difficult to demonstrate complete loss of targeting for some substrates. Our discovery thus puts in place an essential piece of the endoplasmic reticulum targeting puzzle, highlighting how the targeting apparatus of the eukaryotic cell is robust, interlinked and flexible.
2016-11-30 | GSE85686 | GEO
Project description:We obtained transcriptional profiles of third instar eye imaginal disc nuclei with or without endoplasmic reticulum stress using next generation sequencing (NGS). We employed an isolation of nuclei tagged in specific cell type (INTACT) protocol (Ma and Weake, J. of Vis. Exp., 2014) to label nuclear membranes of GMR-GAL4-expressing cells with EGFP. The experimental group also expressed a mutant allele of the membrane visual protein rhodopsin (Rh-1(G69D)), which is known to cause endoplasmic reticulum stress and initiate Unfolded Protein Response (UPR) signaling. The goal of this study was to characterize the transcriptional changes associated with endoplasmic reticulum stress responses in a commonly used platform, the eye imaginal disc.
2021-09-20 | GSE150058 | GEO
Project description:Mutations in the p53 tumor suppressor gene are the most frequent genetic alteration in cancer and often associated with progression from benign to invasive, metastatic stages. Mutations inactivate tumor suppression by p53 and endow the protein with novel gain-of-function (GOF) activities that actively promote tumor progression, metastasis and therapy resistance. By comparative gene expression profiling of p53-mutated and p53-depleted cancer cells we identified ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) as a mutant p53 (mutp53) target gene. A comprehensive pan-cancer analysis revealed a highly significant correlation between GOF p53 mutations and elevated expression of ENTPD5. Mechanistically, regulation of ENTPD5 by mutp53 is mediated by the histone H3 lysine 4 (H3K4) methyltransferase COMPASS complex. ENTPD5 has been shown to function in the endoplasmic reticulum as a UDPase to promote the N-glycosylation and folding of membrane proteins such as growth factor receptors and integrins. We show ENTPD5 to be a mediator of mutp53 GOF activity in clonogenic growth, architectural tissue remodeling, migration, invasion, and lung colonization in an experimental metastasis mouse model. Our study reveals N-glycosylation in the endoplasmic reticulum as a novel mechanism underlying the progression of tumors with mutp53 that could provide new possibilities for treating cancers driven by GOF p53 mutations.
2016-11-29 | E-MTAB-4672 | biostudies-arrayexpress
Project description:Targeting endoplasmic reticulum (ER) stress presents a promising strategy in cancer therapy. We have previously reported that a series of 1,2,4-oxadiazole derivatives induces the degradation of epidermal growth factor receptor and c-Met which are implicated in tumorigenesis. Based on our previous SAR studies, herein, we synthesized EMD37, a novel 1,2,4-oxadiazole derivative, and systematically investigated its anticancer activity.
2023-04-19 | GSE201134 | GEO
Project description:To investigate whether ER stress underpins the secretion of mis-glycosylated glycoproteins by trophoblast, we treated trophoblast-like BeWo cells with the ER stress inducer thapsigargin (Tg), an inhibitor specific for sarco/endoplasmic reticulum Ca2+-ATPase.
2022-12-04 | E-MTAB-10943 | biostudies-arrayexpress