Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA170982 | ENA |
REPOSITORIES: ENA
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Project description:Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively-fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1alpha, ERO1beta and PRDX4, compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly-modest delay in disulfide bond formation in secreted proteins but a profound, five-fold lower procollagen 4 hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content, in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H2O2 generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation and a non-canonical form of scurvy. double and triple mutants and wild type
2012-09-15 | E-GEOD-39492 | biostudies-arrayexpress
Project description:Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively-fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1alpha, ERO1beta and PRDX4, compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly-modest delay in disulfide bond formation in secreted proteins but a profound, five-fold lower procollagen 4 hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content, in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H2O2 generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation and a non-canonical form of scurvy.
2012-09-15 | GSE39492 | GEO
Project description:Genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors.
2014-12-02 | GSE58441 | GEO
Project description:A total of 332 genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors.
2014-12-02 | GSE34736 | GEO
Project description:Background: Metabolic dysregulation has been implicated in bronchopulmonary dysplasia development. Taurine is an essential amino acid for neonates and is critically involved in glucose and fatty acid metabolism. Neonatal tissue obtains taurine mainly through the taurine transporter. The biological role of taurine in neonatal lung development has never been explored. As glucose metabolism mechanistically modulates angiogenesis and angiogenesis is the central player for neonatal lung development, we hypothesize that taurine depletion contributes to bronchopulmonary dysplasia development. Results: Although most genes and proteins for oxidative phosphorylation were enriched in hyperoxia pup lungs, the complex-1 activity decreased. The decrease in taurine-dependent complex-1 core subunits, ND5 and ND6, in hyperoxia lungs reasonably explained the discrepancy. Metabolomics analysis demonstrated decreased lung taurine with increased blood taurine of hyperoxia pups, compatible with the decreased taurine transporter expression. Decreased glycosylation and increased degradation explained the decreased taurine transporter expression. The results of the complementary study using tunicamycin and tauroursodeoxycholic acid studies supported that endoplasmic reticulum stress contributes to decreased taurine transporter expression in hyperoxia lungs. The effect of taurine treatment on reducing endoplasmic reticulum stress, increasing ND5 and ND6 expression, angiogenesis, and, most importantly, the alveolar formation is beneficial to hyperoxia rat pups. Conclusion: Hyperoxia exposure causes endoplasmic reticulum stress, increases taurine transporter degradation, and leads to taurine depletion in the neonatal lungs with subsequent metabolic dysregulation, resulting in poor alveolar formation of the neonatal lungs. We provide evidence of the never-being-reported protective role of taurine in neonatal lung development. The fact that taurine attenuates the severity of bronchopulmonary dysplasia by reducing hyperoxia-induced endoplasmic reticulum stress and mitochondrial dysfunction indicates its therapeutic potential for treating bronchopulmonary dysplasia.
2024-06-01 | GSE249767 | GEO
Project description:T helper (Th) 17 cells form a T cell subset which is crucial to maintain immunity against extracellular bacteria and fungi at epithelial barriers, but Th17 cells are also enriched at sites of inflammation in autoimmune disease. These sites are commonly characterised by adverse environmental conditions which are prone to trigger an ER (endoplasmic reticulum)-stress response. Our lab recently observed that the ER-stress response can be a strong driving force for Th17 cell differentiation. The aim of this RNA-seq project was to characterise the novel Th17 cell population generated by IL-6 and cyclopiazonic acid (CPA)-induced ER stress by transcriptional profiling of ER-stress generated and conventional Th17 cells. For this purpose nave IL17A-Cre Rosa-RFP CD4 T cells were cultured with a combination of Interleukin 6 with Transforming growth factor (TGF) or CPA for three days. Then, RFP-positive Th17 cells from four different experiments were enriched for by FACS sorting. Following RNA isolation using QIAGEN's RNA Mini Plus Kit and rRNA depletion accomplished with the NEBNext rRNA Depletion Kit, RNA-seq libraries were generated using the undirectional NEBNext Ultra RNA Library Prep Kit for Illumina. The libraries were sequenced as 75bp paired-end reads on a NextSeq 500 sequencer and analysed using QIAGEN's Biomedical Workbench.
2017-06-14 | E-MTAB-5692 | biostudies-arrayexpress
Project description:COL4A3/A4/A5 mutations have been identified as critical causes of Alport syndrome and other genetic chronic kidney diseases. However, the underlying pathogenesis remains unclear, and specific treatments are lacking. Here, we constructed a transgenic Alport syndrome mouse model by generating a mutation (Col4a3 p.G799R) identified previously from one large Alport syndrome family into mice. We observed that the mutation caused a pathological decrease in intracellular and secreted collagen IV α3α4α5 heterotrimers. The mutant collagen IV α3 chains abnormally accumulated in the endoplasmic reticulum and exhibited defective secretion, leading to persistent endoplasmic reticulum stress in vivo and in vitro. RNA-seq analysis revealed that the MyD88/p38 MAPK pathway plays key roles in mediating subsequent inflammation and apoptosis signaling activation. Treatment with tauroursodeoxycholic acid, a chemical chaperone drug that functions as an endoplasmic reticulum stress inhibitor, effectively suppressed endoplasmic reticulum stress, promoted secretion of the α3 chains, and inhibited the activation of the MyD88/p38 MAPK pathway. Tauroursodeoxycholic acid treatment significantly improved renal function in vivo. These results partly clarified the pathogenesis of renal injuries associated with Alport syndrome, especially in glomeruli, and suggested that tauroursodeoxycholic acid might be useful for the early clinical treatment of Alport syndrome.
2024-08-28 | GSE261588 | GEO
Project description:DNA damage and metabolic disorders are intimately linked with premature disease onset but the underlying mechanisms remain poorly understood. Persistent DNA damage accumulation in tissue-infiltrating macrophages carrying an ERCC1-XPF DNA repair defect (Er1F/-) riggers Golgi dispersal, dilation of endoplasmic reticulum, autophagy and exosome biogenesis leading to the secretion of extracellular vesicles (EVs) in vivo and ex vivo.
2019-11-04 | E-MTAB-8439 | biostudies-arrayexpress
Project description:Within the family of NADPH oxidases, Nox4 is unique as it is predominantly localized in the endoplasmic reticulum, has constitutive activity and generates H2O2. We hypothesize that these features are consequences of a so far unidentified Nox4-interacting protein. Interacting proteins were screened by quantitative SILAC-Co-immunoprecipitation in HEK293 cells stably overexpressing Nox4. By this technique, several interacting proteins were identified with calnexin showing the most robust interaction.
2017-03-29 | MSV000080772 | MassIVE
Project description:PHOSPHATIDIC ACID PHOSPHOHYDROLASE (PAH) catalyses the conversion of phosphatidic acid to diacylglycerol. Disruption of two gene encoding this enzyme in Arabidopsis thaliana results in increased phosphatidylcholine synthesis and proliferation of the endoplasmic reticulum (Eastmond et al., [2010] Plant Cell 22: 2796). We performed microarray analysis on two week old wild type Arabidopsis plants and the pah1 pah2 double mutant using the Ath1 chip to determine what effect the double mutation has on global gene expression.
2015-09-01 | E-MTAB-3253 | biostudies-arrayexpress