Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Global transcriptomic profiling of ischemic/reperfusion injury in an in vivo Gpx1 -/- transgenic mouse model.

ABSTRACT: Glutathione peroxidase (Gpx) is a selenium-containing enzyme that catalyses the reduction of a variety of biological peroxides at the expense of reduced glutathione (GSH). Gpx1 is the most abundant isoform and its role has been implicated in neurodegenerative disorders such as ParkinsonM-bM-^@M-^Ys disease (PD), dementia with Lewy bodies tissue (DLB) (Power and Blumbergs, 2009) and traumatic brain injury (Tsuru-Aoyagi et al., 2009). Due to its high abundance, mutation of the Gpx1 allele would lower overall Gpx activity in the brain significantly. Gpx1 knockout (Gpx1-/-) mice do not show overt phenotypic differences, but all indications suggest that these mice are in a chronic M-bM-^@M-^\pro-oxidantM-bM-^@M-^] state (Cheng et al. 1999; de Haan et al. 2004). Indeed, a recent study from our laboratory illustrated that the absence of Gpx1 exacerbated stroke injury via increased ROS production and vascular permeability (Wong et al. 2008). Furthermore, Gpx1-/- mice demonstrated an increase in caspase-3 activation and greater infarct volume (Crack et al. 2001) Microarray analysis was performed on the right striatum and cortex(corresponded to infarct area) of post-I/R injured brain tissues of Gpx1 -/- brains using Illumina mouse Ref8 V2 genechips. Suture-induced middle cerebral artery occlusion was induced for 2h followed by reperfusion, with tissue extraction taking place 2h, 8h and 24h post-reperfusion (n=4 respectively). Sham controls were included in this study too (n=4 respectively).

ORGANISM(S): Mus musculus

SUBMITTER: Minghui Jessica Chen

PROVIDER: E-GEOD-23162 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic-reperfusion injury.

Chen Minghui Jessica MJ Wong Connie H Y CH Peng Zhao Feng ZF Manikandan Jayapal J Melendez Alirio J AJ Tan Theresa M TM Crack Peter J PJ Cheung Nam Sang NS

Free radical biology & medicine 20101228 6

Transient cerebral ischemia often results in secondary ischemic/reperfusion injury, the pathogenesis of which remains unclear. This study provides a comprehensive, temporal description of the molecular events contributing to neuronal injury after transient cerebral ischemia. Intraluminal middle cerebral artery occlusion (MCAO) was performed to induce a 2-h ischemia with reperfusion. Microarray analysis was then performed on the infarct cortex of wild-type (WT) and glutathione peroxidase-1 (a maj ...[more]

PMID: 21193029

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Project description:Coronary heart disease is the leading cause of death worldwide. After an acute myocardial infarction, early reperfusion reduces infarct size, which correlates with improved clinical outcomes. Paradoxically, reperfusion although relieving ischemia, accelerates apoptosis in injured cardiomyocytes, which has led to the view that myocardial salvage is futile beyond the first few hours of reperfusion. In murine hearts subjected to 90 min of coronary artery occlusion and then 48 h of reperfusion, we show transient activation of intrinsic prosurvival insulin-like growth factor-1 (IGF-1) signaling. In these hearts, acute IGF-1 receptor inhibition decreases the abundance of prosurvival signaling molecules, and markedly activates caspase-3, a potent effector of apoptosis, in infarct border zone cardiomyocytes. We found that mouse mast cell protease-4 (MMCP-4) degraded IGF-1 in vitro by a novel catalytic activity of chymases. In vivo, this degradation, which is triggered by mast cell infiltration into the peri-infarct region and MMCP-4 extravasation, between 48 and 72 h post-ischemia/reperfusion (I/R), attenuates IGF-1 prosurvival signaling. In MMCP-4-deficient mice, while infarct size is not reduced at 24 h post-I/R, at 72 h post-I/R myocardial IGF-1 levels and signaling are increased, resulting in activation of the survival kinases Akt and ERK, inhibition of caspase-3, and reduced myocardial cell death. As a consequence, I/R-mediated loss of viable myocardium, adverse cardiac remodeling and contractile impairment are markedly reduced. Cardiomyocyte survival with consequent myocardial salvage may thus be possible even days after an ischemic insult, making them a novel therapeutic target for delayed cardioprotective therapy. Group 1 is wild type C57Bl6 uninjured hearts. These mice were not undergone any surgery and used as controls. Group 2 are wild type C57Bl6 72 h post-ischemia reperfusion (IR) injury hearts. These mice for subjected to ischemia reperfusion (IR) involving 90 min of left anterior descending coronary artery occlusion followed by reperfusion for 3 days or 72 h.

Project description:To reveal the comparative pharmacological mechanism of differential compounds and its combination, we used a custom cNDA microarray to screen gene expression on ischemia mouse hippocampus. Cerebral ischemia was induced in anesthetized mice by urethane (1.5g/kg, i.p) to 38-48g male or female mice by occlusion of the middle cerebral artery (MCA) for 15 minutes twice with microvascular clips, followed by reperfusion for 10 minutes after the first occlusion. Experimental animal were divided into groups: Sham-operated, vehicle (M3,ischemic mice 3 hour;12 hour;24 hour),Baicalin(BA) (5mg/ml), Jasminoidin(JA) (25mg/ml),Jasminoidin(H) (50mg/ml),Cholic acid(CA) (7mg/ml),Concha margaritifera(CM) (50mg/ml), Nimodipine (NI) (50mg/ml),and JA+BA, JA+CA, JA+BA+CA, JA+BA+CA+CM. The prescription of combination therapies was composed of the same ratio on every compound. Treated compound dosage according to 0.2ml physic liquor/100g mouse or rat body weight treated at 1.5h post operation given through tail vein. Sham-operated mice underwent identical procedures except therapy were vehicle (2ml/kg; 100% DMSO). Infarct Volume and Neurological Score were tested to display variation on comeout change. Hippocampus (subfields CA1-4 of Ammon's horn) were carefully dissected out from re-anesthetized mice under RNAase-free conditions, flash frozen and stored at -75 C. Total RNA of each sample was extracted with Trizol reagent (Invitrogen, procedure according to the instruction manual). Three animals per group were pooled and homogenized in denaturing solution with a Polytron. Three pooled per group and nine times repeted microarray experiments of each pooled were preformed. Each microarray contained 374 cDNA derived from cDNA library of mouse brain (Invitrogen, Cat.1065-025). Plasmid magnified using Invitrogen provided library. Design and synthesize Primer according the information provided by selected genes.Total gene segment is 416, two of them is control(lambda-A and pUC19). The criterion of qualified PCR extending is: the total gained volume of the purpose strap DNA is greater or equal to 7?g;the purpose strap DNA gained volume/total DNA gained volume is greater or equal to 80%.Finally, the DNA concentration is adjusted to 0.5 ?g/ ?l.After refinded PCR_for every gene, 2?l DNA solution was taken to proceeding electrophoresis on the electrophoresis condition of 2%Gel.Then fix quantify analysis according electrophoresis photo have taken.Choosing 5 PCR refined products sequencing from two direction after amplification.These 5 genes all chosen from UniGene sample which marked by ?,one of them is used Dalian ? as cyclostyle to amplification.The five sequence genes was certified as aimed gene segment by Blast(Completed in TaKaRa(Dalian))

Dataset Information

Global transcriptomic profiling of ischemic/reperfusion injury in an in vivo Gpx1 -/- transgenic mouse model.

Publications

A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic-reperfusion injury.

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