A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion

Mitsios, Nicholas; Saka, Mohamad; Krupiński, Jerzy; Pennucci, Roberta; Sanfeliu, Coral; Wang, Qiuyu; Rubio, Francisco; Gaffney, John; Kumar, Patricia; Kumar, Shant; Sullivan, Matthew; Slevin, Mark

doi:10.1186/1471-2202-8-93

Cited by 46 publications

(48 citation statements)

References 56 publications

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“…Likewise, the ischemia-induced downregulation of synaptophysin and SNAP-25 observed in hippocampal neurons of gerbils could be due to presynaptic degeneration that preceded the delayed neuronal death [48]. In rats, synaptotagmin mRNA was downregulated during early recirculation after focal cerebral ischemia [49].…”

Section: Discussionmentioning

confidence: 98%

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

et al. 2016

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After ischemic stroke, cell damage propagates from infarct core to surrounding tissues (penumbra). To reveal proteins involved in neurodegeneration and neuroprotection in penumbra, we studied protein expression changes in 2-mm ring around the core of photothrombotic infarct induced in the rat brain cortex by local laser irradiation after administration of Bengal Rose. The ultrastructural study showed edema and degeneration of neurons, glia, and capillaries. Morphological changes gradually decreased across the penumbra. Using the antibody microarrays, we studied changes in expression of >200 neuronal proteins in penumbra 4 or 24 h after focal photothrombotic infarct. Diverse cellular subsystems were involved in the penumbra tissue response: signal transduction pathways such as protein kinase Bα/GSK-3, protein kinase C and its β1 and β2 isoforms, Wnt/β-catenin (axin1, GSK-3, FRAT1), Notch/NUMB, DYRK1A, TDP43; mitochondria quality control (Pink1, parkin, HtrA2); ubiquitin-mediated proteolysis (ubiquilin-1, UCHL1); axon outgrowth and guidance (NAV-3, CRMP2, PKCβ2); vesicular trafficking (syntaxin-8, TMP21, Munc-18-3, synip, ALS2, VILIP1, syntaxin, synaptophysin, synaptotagmin); biosynthesis of neuromediators (tryptophan hydroxylase, monoamine oxidase B, glutamate decarboxylase, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter); intercellular interactions (N-cadherin, PMP22); cytoskeleton (neurofilament 68, neurofilament-M, doublecortin); and other proteins (LRP1, prion protein, β-amyloid). These proteins are involved in neurodegeneration or neuroprotection. Such changes were most expressed 4 h after photothrombotic impact. Immunohistochemical and Western blot studies of expression of monoamine oxidase B, UCHL1, DYRK1A, and Munc-18-3 confirmed the proteomic data. These data provide the integral view on the penumbra response to photothrombotic infarct. Some of these proteins can be potential targets for ischemic stroke therapy.

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Section: Discussionmentioning

confidence: 98%

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

et al. 2016

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“…A closer look at the gene list revealed more angiogenesis-related genes as well as hypoxia/HIF1α target genes among the genes upregulated in the nonresponder models, as for example, the carbonic anhydrases IX and XII (CA9 and CA12), the BH3 only protein BNIP3L, the glucose transporter SLC2A1 (also known as GLUT1), the integrin ITGA6, matrix metallopeptidase 11 (MMP11), and Jumonji domain containing 2B (JMJD2B) (Supplementary Table S5, refs. [30][31][32][33][34]. Examples of gene expression levels of these genes are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Comparative Profiling of the Novel Epothilone, Sagopilone, in Xenografts Derived from Primary Non–Small Cell Lung Cancer

Hammer

Sommer²,

Fichtner³

et al. 2010

Clinical Cancer Research

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Purpose: Characterization of new anticancer drugs in a few xenograft models derived from established human cancer cell lines frequently results in the discrepancy between preclinical and clinical results. To take the heterogeneity of tumors into consideration more thoroughly, we describe here a preclinical approach that may allow a more rational clinical development of new anticancer drugs.Experimental Design: We tested Sagopilone, an optimized fully synthetic epothilone, in 22 well-characterized patient-derived non-small cell lung cancer models and correlated results with mutational and genome-wide gene expression analysis.

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“…1a). Then to identify novel therapeutic targets to promote recovery after stroke, we collected highthroughput experimental data on expression profiling of transcripts induced in stroke brain from published papers [9][10][11][12][13]. Based on these microarray data, we then picked up the representative transcripts of neural plasticityrelated genes (GAP43, Neuritin, VGF, Arc, PC3, hsp90) induced after stroke mostly within 24 h after injury and performed the long-term (1-28 days) expression profiling analyses by real-time PCR assay using RNAs from the total cortices of photothrombotic or sham-operated brain on the ipsilateral side (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The mechanisms of neural plasticity after stroke could be similar to those during development, including activity-dependent rewiring (dynamic axon and dendrite arbor growth) and synaptic plasticity (functional modulation of existing synapses as well as structural modulation) [3][4][5][6][7][8]. A variety of high-throughput expression analyses including microarray and real-time PCR using rodent, primate, and human stroke brain have shown that many of the genes and proteins critical for neural differentiation, apoptosis and survival, neurogenesis, synaptogenesis, and synaptic plasticity are induced after stroke as observed in the developing brain [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 98%

VGF, Which Is Induced Transcriptionally in Stroke Brain, Enhances Neurite Extension and Confers Protection Against Ischemia In Vitro

Sakamoto

Miyazaki

Kitajo

et al. 2015

Transl. Stroke Res.

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Ischemic stroke is a devastating neural event as currently no therapies other than physical rehabilitation are available to enhance recovery after stroke. To identify endogenous mediators to repair stroke brain, we performed the expression profiling analysis of transcripts in the mouse photothrombotic stroke brain. Based on real-time PCR analysis, we found VGF, identified as a nerve growth factor (NGF)-regulated transcript, was induced transcriptionally in stroke brain at 1-7 days after insult. The immunoreactivites of VGF were observed in the neurons around the ischemic core of stroke brain. Experiments with various inhibitors and plasmid transfections indicated that cAMP response element binding protein-mediated complex signaling pathways are possibly implicated in the NGF-mediated VGF expressions in vitro. Furthermore, the over-expression of VGF promoted neurite extensions and conferred protections from ischemic stress in vitro. These findings raise the possibility the application of VGF could be one of the promising therapeutic strategies to enhance recovery after stroke.

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A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion

Abstract: Background: Altered gene expression is an important feature of ischemic cerebral injury and affects proteins of many functional classes. We have used microarrays to investigate the changes in gene expression at various times after middle cerebral artery occlusion in human and rat brain.

Cited by 46 publications

References 56 publications

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

Comparative Profiling of the Novel Epothilone, Sagopilone, in Xenografts Derived from Primary Non–Small Cell Lung Cancer

VGF, Which Is Induced Transcriptionally in Stroke Brain, Enhances Neurite Extension and Confers Protection Against Ischemia In Vitro

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