The effect of XUESAITONG on gene expression profile after focal cerebral ischemia in rats
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Xiaohui Fan
PROVIDER: E-GEOD-61616 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Analysis of changes in gene expression induced by a transient (90') middle cerebral artery occulsion, at several time points post stroke induction, with the effect of a treatment with the drug FK506 studied at a single time point.
2010-06-19 | E-MEXP-2222 | biostudies-arrayexpress
Project description:We obtained the profiles of neuronal phosphoproteome after cerebral ischemia and reperfusion by isolating mice hippocampus. Hippocampus combined from either nine sham or nine focal cerebral ischemia 1.5 h and reperfusion 24 h (IR) mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. In total, we quantified 7,865 phosphopeptides,179 phosphorylation sites of 129 proteins were upregulated and 843 phosphorylation sites of 494 proteins were downregulated in hippocampus during cerebral ischemia 2 h compare with sham operation.
2024-02-15 | PXD033851 | Pride
Project description:We obtained the profiles of neuronal proteome after cerebral ischemia and reperfusion by isolating mice hippocampus. Hippocampus combined from either nine sham or nine focal cerebral ischemia 1.5 h and reperfusion 24 h (IR) mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. In total, we quantified 5,059 proteins. We identified 142 differentially expressed proteins (t-test, p-value<0.05) after IR compared to sham groups. The results showed that 92 proteins were upregulated, and 50 proteins were downregulated after IR compared to sham groups. Gene ontology (GO) enrichment analysis of differentially expressed proteins between sham and IR groups. The results showed that the biological process of most of upregulated genes linked with immune inflammatory related responses were increased. And KEGG pathway analysis for upregulated genes showed that multiple immune inflammatory response pathways also increased significantly, such as TNF-signaling, NF-κB signaling and cytokine-cytokine receptor interaction, as well as NOD-like receptor signaling, and toll-like receptor signaling.
2024-02-15 | PXD033938 | Pride
Project description:Sleep deprivation (SD) performed before stroke induces an ischemic tolerance state as observed in other forms of preconditioning. As the mechanisms underlying this effect are not well understood we used DNA oligonucleotide microarray analysis, to identify the genes and the gene-pathways underlying SD preconditioning. Gene expression was analyzed 3 days after stroke surgery in four experimental groups: i) SD performed before focal cerebral ischemia induction; ii) SD performed before Sham surgery; iii) IS without SD; and iv) Sham surgery without SD. SD was performed by gentle handling during the last 6h of the light period and ischemia was induced immediately after. Stroke induced a massive alteration in gene expression both in sleep deprived and non-sleep deprived animals. However, compared to animals that underwent ischemia alone, SD induced a general reduction in transcriptional changes with a reduction in the upregulation of genes involved in cell cycle regulation and immune response. Moreover an upregulation of a new neuroendocrine pathway which included melanin concentrating hormone, glycoprotein hormones-M-kM-1-polypeptide and hypocretin was observed exclusively in rats sleep deprived before stroke. Our data indicate that SD before stroke reprogrammed the signaling response to injury. The inhibition of cell cycle regulation and inflammation are neuroprotective mechanisms reported also for other forms of preconditioning treatment whereas the implication of the neuroendocrine function is novel and has never been described before. These results therefore provide new insights into neuroprotective mechanisms involved in ischemic tolerance mechanisms.
2015-10-30 | E-MTAB-3148 | biostudies-arrayexpress
Project description:This data set shows dramatic changes in gene expression in microglia isolated from C57Bl6/J mice subjected to transient middle cerebral artery occlusion, as compared to those subjected to sham surgery. Mice deficient in Mincle (Clec4e-/-) showed significantly improved injury outcomes 3 and 7 days after transient middle cerebral artery occlusion. However, when comparing changes in gene expression in microglia 24 hours after blood reperfusion, there were no differences between wild-type and Clec4e-/- mice, indicating that Mincle does not participate in early microglial activation. Wild type and Mincle knock-out (Clec4e-/-) mice. After 1 h of transient middle cerebral artery occlusion (tMCAO) and 24 h of reperfusion, mice were perfused with PBS, their brains dissected, and 2 ipsilesional hemispheres (with cerebellum and brainstem removed) pooled for microglia isolation. For sham-operated animals, the whole forebrain was used and brains were not pooled. After myelin separation by Percoll gradient centrifugation, around 80,000 CD45intermediate, CD11b+ microglial cells were sorted from each sample. Sham samples n=3, tMCAO samples n=5.
2016-03-24 | E-GEOD-77986 | biostudies-arrayexpress
Project description:profiling gene transcription in a mouse model of permanent focal cerebral ischemia that was induced by middle cerebral artery occlusion (MCAO)
2009-03-07 | E-TABM-655 | biostudies-arrayexpress
Project description:We obtained the profiles of neuronal phosphoproteome after cerebral ischemia onset by isolating mice hippocampus. Hippocampus combined from either ten sham or ten focal cerebral ischemia 2 h mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. Five percent of the pool was used for whole proteome analysis, and the remaining 95% was subjected to phosphoproteome profiling. In total, we quantified 5,174 proteins and 9,062 phosphopeptides. Interesting, 21 proteins were upregulated and 7 proteins were downregulated in hippocampus lysates of cerebral ischemia 2 h relative to sham base on fold change. S100a9, Alpha-2-HS-glycoprotein (Ahsg), Fibrinogen beta chain (Fga) and Complement Component C3(c3) are the top significantly changed, which were highly consistent with previous reports in cerebral ischemia injury. Using wolfpsort software to analysis the Subcellular Location, 57% of detected proteins were location to extracellular, 15% were cytoplasmic protein, another 11% were transport to nucleus, and the others were location to plasma membranes (10%), mitochondria (4%) and endoplasmic reticulum (3%). Moreover,184 phosphorylation sites of 135 proteins were upregulated and 689 phosphorylation sites of 420 proteins were downregulated in hippocampus during cerebral ischemia 2 h compare with sham operation. Employing wolfpsort software analysis the subcellular location, 50% of phosphorylated proteins were location to nucleus, 26% were cytoplasmic protein, another 16% were transport to plasma membranes, and the others were location to mitochondria (4%), extracellular (3%) and cytoskeleton (1%). Motif analysis showed that 85% were belongs to serine-type phosphorylation, about 14 were threonine-type phosphorylation and 1% were tyrosine-type phosphorylation.
2022-03-14 | PXD027145 | Pride
Project description:Posttranslational modifications with ubiquitin alter protein function and stability, thereby regulating cell homeostasis and viability, particularly under stress. Ischemic stroke induces protein ubiquitination at the periphery of the ischemic territory, wherein cells remain viable. Revealing the identity of ubiquitinated proteins, their cellular location, and the functional consequences of ubiquitin modification may shed light on the role of ubiquitination in ischemic injury. Here, we employed a proteomics approach to identify proteins ubiquitinated following ischemic stroke, induced by transient middle cerebral artery occlusion (tMCAO) in mice. We detected increased ubiquitination of 198 proteins, many of which localize to the postsynaptic density (PSD) of glutamatergic neurons. Among these were proteins essential for maintaining PSD architecture, such as PSD93, PSD95 and Shank3, as well as NMDA and AMPA receptor subunits. The largest enzymatic group at the PSD with high post-ischemic ubiquitination levels were kinases, such as CaMKII, PKC, Cdk5, and Pyk2, the aberrant activity of which contributes to post-ischemic neuronal death. Concurrent phospho-proteomics revealed altered phosphorylation patterns associated with the PSD, indicative of modified PSD kinase activity following stroke. CaMKII, PKC, and Cdk5 activity was decreased while Pyk2 activity was increased at the PSD after stroke, accompanied by the hypo- and hyper-phosphorylation of downstream targets, respectively. Removal of ubiquitin restored kinases’ activity to pre-stroke levels, identifying ubiquitination as the responsible molecular mechanism for post-ischemic kinase regulation. These findings unveil a previously unrecognized role of post-ischemic ubiquitination in the regulation of essential kinases involved in ischemic injury, and presents targeting ubiquitination as a potential new avenue for the treatment of ischemic stroke.
2023-09-06 | PXD042951 | Pride
Project description:Permanent middle cerebral artery occlusion (PMCAO) mouse model has been established and used by our group with a focus on systematically investigating effects of the neuropeptide pituitary adenylate-cyclase activating polypeptide (PACAP38) on the ischemic brain. Using an intracerebroventrically PACAP38 (1 pmol) injection over a control saline (0.9% sodium chloride, NaCl) treatment, we have been successful in generating a vast inventory of gene expression data in both whole hemispheres and specific brain regions of infract/ischemic core (IC) and penumbra (P) with high-throughput Agilent whole genome 4 × 44 K oligo DNA microarray chips. In this study, we first perform a specific analysis of the gene expression in the IC and P compared to the healthy control regions to know the gene profile status of the progression of the IC. We will use this data together with generated biological function and network analysis from our previous studies, and present new insight into the potential mechanism behind PACAP38 neuroprotective function in the ischemic brain. Three mice each in PMCAO groups for ischemic core and penumbra regions in ischemic brain over corresponding controls were used, respectively, that exhibited neurological grades G1 and G2 for the subsequent downstream analysis. Ischemic core and penumbra regions and corresponding healthy core and penumbra were carefully removed with a sterile scalpel, and placed in 2 ml Eppendorf tubes. Samples were then quickly immersed in liquid nitrogen and stored in -80 ºC prior to further analysis. Whole genome DNA microarray analysis was performed on a 4x44K, Agilent DNA Microarray chip.
2015-03-31 | E-GEOD-67421 | biostudies-arrayexpress
Project description:Our group has been systematically investigating effects of the neuropeptide pituitary adenylate-cyclase activating polypeptide (PACAP) on the ischemic brain. To do so, we have established and utilizing the permanent middle cerebral artery occlusion (PMCAO) mouse model, where PACAP38 (1 pmol) injection is given intracerebroventrically in comparison to a control saline (0.9% NaCl) injection, in conjunction with high-throughput DNA microarray analysis. In previous studies, we have accumulated a large volume of data (gene inventory) from the whole brain (ipsilateral and contralateral hemispheres) by this approach. In our latest research, we have targeted specifically infract/ischemic core (hereafter IC) and the penumbra (hereafter P) post-PACA38 injection, for re-examining the transcriptome at 6 and 24 h post-treatment. The aim of the current study is simple M-bM-^@M-^S to delineate the specificity of expression and localization of differentially expressed molecular factors influenced by PACAP38. Prior to this highly expensive and time-consuming omic analysis, we checked the validity of our hypothesis and experimental strategy wherein, ischemic core and penumbra were carefully sampled and compared to the corresponding contralateral (healthy) IC and P regions at 6 and 24 h, post PACAP38 or saline injections to reveal expected differences in gene and protein expression by traditional reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses, respectively (Hori et al., 2014). Our present results using the mouse 4x44K whole genome DNA chip reveal numerous changes (M-bM-^IM-'/M-bM-^IM-& 1.5/0.75-fold) at both 6 h (654 and 456, and 522 and 449 up- and down-regulated genes for IC and P, respectively; and 24 h (2568 and 2684, and 1947 and 1592 up- and down-regulated genes for IC and P, respectively) after PACAP38 treatment. Using bioinformatics analysis by pathway- or specific-disease-state focused gene classifications and Ingenuity Pathway Analysis (IPA), these genes were functionally classified and discussed. Taken together, the DNA microarray analysis provides not only a great resource for further study, but also reinforces the importance of region-specific analyses in genome-wide identification of target molecular factors that might play a role in the neuroprotective function of PACAP38. In the present study, we used three mice each in PMCAO groups for PACAP38 and saline injections, respectively, that exhibited neurological grades G1 and G2 for the subsequent downstream analysis. Six or 24 h post-injection of PACAP38 or saline, the mice were removed from their cages, decapitated, and their brains carefully removed on ice. The right (ipsilateral; ischemic) and left (contralateral) hemispheres were dissected, and from each hemisphere the ischemic core and penumbra regions and corresponding healthy core and penumbra were carefully removed with a sterile scalpel, and placed in 2 ml Eppendorf tubes. The samples were then quickly immersed in liquid nitrogen and stored in -80 M-BM-:C prior to further analysis. Effect of the intracerebroventricular PACAP38 administration into ischemic mouse brain was evaluated at the molecular level in the ischemic core and penumbra of ipsilateral (right) hemisphere over the saline injection by whole genome DNA microarray analysis (4x44K, Agilent).
2014-10-31 | E-GEOD-62884 | biostudies-arrayexpress