Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA102823 | ENA |
REPOSITORIES: ENA
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Project description:The hepatic endoplasmic reticulum contains a series of enzymes that oxidize and conjugate lipid and steroids. Together, these enzymes form a molecular machine that plays key roles in the metabolism of both endogenous and xenobiotic compounds. To characterize this molecular machine, we used quantitative proteomics to assess the frequency of occurrence of detected peptides within each primary sequence, leading to the assessment of the relative abundances of 137 of these proteins. These 137 proteins include over 38 different cytochrome P450s, 11 glucuronosyltransferases, and 9 carboxylesterases. Our sensitive approach was able to detect P450 allelic isoforms which differ by only a single amino acid and clearly resolved 4 splice variants of the glucuronosyltransferases. We identified a cytosolically-exposed DID motif for 3 cytochrome P450s that were located with high abundance in the Golgi apparatus as well the lack of a C-terminal HXEL motif for the sole carboxylesterase highly abundant in the Golgi. Using gene expression microarrays, we also characterized the hepatic transcriptome, and a comparison of proteomics and transcriptomics indicated a requirement for both technologies in order to provide insight into protein families of drug detoxification. In this way, a major hurdle of hepatotoxicity related to drug development may be overcome. Experiment Overall Design: Four replicate Sprague-Dawley rats were assessed, each on an individual microarray.
2009-11-28 | E-GEOD-9226 | biostudies-arrayexpress
Project description:Transcriptome response to endoplasmic reticulum stress in rat oligodendrocyte precursor cells
| PRJNA322543 | ENA
Project description:Endoplasmic reticulum proteins impact penetrance in a pink1-mutant Drosophila model
| PRJNA1214414 | ENA
Project description:The hepatic endoplasmic reticulum contains a series of enzymes that oxidize and conjugate lipid and steroids. Together, these enzymes form a molecular machine that plays key roles in the metabolism of both endogenous and xenobiotic compounds. To characterize this molecular machine, we used quantitative proteomics to assess the frequency of occurrence of detected peptides within each primary sequence, leading to the assessment of the relative abundances of 137 of these proteins. These 137 proteins include over 38 different cytochrome P450s, 11 glucuronosyltransferases, and 9 carboxylesterases. Our sensitive approach was able to detect P450 allelic isoforms which differ by only a single amino acid and clearly resolved 4 splice variants of the glucuronosyltransferases. We identified a cytosolically-exposed DID motif for 3 cytochrome P450s that were located with high abundance in the Golgi apparatus as well the lack of a C-terminal HXEL motif for the sole carboxylesterase highly abundant in the Golgi. Using gene expression microarrays, we also characterized the hepatic transcriptome, and a comparison of proteomics and transcriptomics indicated a requirement for both technologies in order to provide insight into protein families of drug detoxification. In this way, a major hurdle of hepatotoxicity related to drug development may be overcome. Keywords: steady-state mRNA levels
2009-11-24 | GSE9226 | GEO
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:The SND proteins constitute an alternative targeting route to the endoplasmic reticulum
| PRJNA339062 | ENA
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: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:Exosomes are cell membrane-derived endoplasmic reticulum measuring 30 to 120 nm, which are secreted from various cells including cancer cells, and consist of lipids, proteins, mRNAs, and microRNAs (miRNAs). Tumor-derived exosomes are involved in tumor progression by delivering various factors to neighboring cells and promoting intercellular communication. MiRNA is a non-coding RNA consisting of 20-24 nucleotides that binds to the 3'UTR region of the target gene with a complementary nucleotide sequence during gene expression to degrade target mRNA or inhibit translation into target protein. In our study, exosomal miRNA profiling was utilized as a crucial technique to analyze the mechanisms of intercellular communication in tumor malignancy
2024-03-27 | GSE260909 | GEO
Project description:Mutations in the endoplasmic reticulum (ER) chaperone calreticulin (CALR) are common in myeloproliferative neoplasm (MPN) patients, activate the thrombopoietin receptor (MPL), and mediate constitutive JAK/STAT signaling. The mechanisms by which CALR mutations cause myeloid transformation are incompletely defined. We employed mass spectrometry proteomics to identify novel CALR-mutant interacting proteins. Mutant CALR caused mislocalization of binding partners and increased recruitment of FLI1, ERP57 and CALR to the MPL promoter to enhance transcription. CALR 52 mutant was also found to increase genome-wide recruitment of Fli1 to the chromatin. Overall, these results show that type 1 CALR mutant modulates Fli1 cellular localization and recruitment.
2018-09-19 | GSE120134 | GEO