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Comparison of gene expression profiles of anaplastic glioma with or without the mutated IDH1/2 gene

ABSTRACT: To examine the NRF2 activity in anaplastic glioma with mutated IDH1/2, we conducted the microarray analysis to measure the expression levels of representative NRF2 target genes, including NQO1, HMOX1, GCLM, TXNRD1, and PRDX1. 12 anaplastic gliomas with or without mutated IDH1/2.

ORGANISM(S): Homo sapiens

SUBMITTER: Masayuki Kanamori

PROVIDER: E-GEOD-52942 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Activation of the NRF2 pathway and its impact on the prognosis of anaplastic glioma patients.

Kanamori Masayuki M Higa Tsuyoshi T Sonoda Yukihiko Y Murakami Shohei S Dodo Mina M Kitamura Hiroshi H Taguchi Keiko K Shibata Tatsuhiro T Watanabe Mika M Suzuki Hiroyoshi H Shibahara Ichiyo I Saito Ryuta R Yamashita Yoji Y Kumabe Toshihiro T Yamamoto Masayuki M Motohashi Hozumi H Tominaga Teiji T

Neuro-oncology 20141010 4

<h4>Background</h4>Nuclear factor erythroid 2-related factor 2 (NRF2) plays pivotal roles in cytoprotection. We aimed at clarifying the contribution of the NRF2 pathway to malignant glioma pathology.<h4>Methods</h4>NRF2 target gene expression and its association with prognosis were examined in 95 anaplastic gliomas with or without isocitrate dehydrogenase (IDH) 1/2 gene mutations and 52 glioblastomas. To explore mechanisms for the altered activity of the NRF2 pathway, we examined somatic mutatio ...[more]

PMID: 25304134

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Comparison of gene expression profiles of anaplastic glioma with or without the mutated IDH1/2 gene

Project description:To examine the NRF2 activity in anaplastic glioma with mutated IDH1/2, we conducted the microarray analysis to measure the expression levels of representative NRF2 target genes, including NQO1, HMOX1, GCLM, TXNRD1, and PRDX1.

2013-12-04 | GSE52942 | GEO

Acetylation changes in NQO1 overexpression in Mouse Skeletal Mucscle

Project description:In this manuscript we have explored the role of both Nrf2 and NQO1 in protection against diet-induced metabolic syndrome and demonstrate that both Nrf2 and NQO1 provide protection against HFD-induced adverse phenotypes in a mouse model

2021-09-08 | PXD015070 | Pride

Metabolic changes related to the IDH1 mutation in gliomas preserve TCA-cycle activity: an investigation at the protein level

Project description:The discovery of the IDH1 R132H (IDH1 mut) mutation in low-grade glioma and the associated change in function of the IDH1 enzyme has increased the interest in glioma metabolism. In an earlier study, we found that changes in expression of genes involved in the aerobic glycolysis and the TCA-cycle are associated with IDH1 mut. Here we apply proteomics to FFPE samples of diffuse gliomas with or without IDH1 mutations, in order to map changes in protein levels associated with this mutation. We observed significant changes in the enzyme abundance associated with aerobic glycolysis, glutamate metabolism and the TCA-cycle in IDH1 mut gliomas. Specifically, the enzymes involved in the metabolism of glutamate, lactate and enzymes involved in the conversion of α-ketoglutarate were increased in IDH1 mut gliomas. In addition, the bicarbonate transporter (SLC4A4) was increased in IDH1 mut gliomas, supporting the idea that a mechanism preventing intracellular acidification is active. We also found that enzymes that convert proline, valine, leucine and isoleucine into glutamate were increased in IDH1 mut glioma. We conclude that in IDH1 mut glioma metabolism is rewired (increased input of lactate and glutamate) to preserve TCA cycle activity in IDH1 mut gliomas.

2020-03-09 | PXD016697 | Pride

Expression profile of cortices, hippocampi and brainstems of Nrf2 knockout mice under unstressed conditions

Project description:Microarray analysis of cortices, hippocampi and brainstems of Nrf2 knockout mice, Three independent RNAs from cortices, hippocampi and brainstems of Nrf2 knockout and wild-type control mice were used for the microarray analyses.

2013-08-05 | E-GEOD-47587 | biostudies-arrayexpress

High expression genes in urethane-induced lung tumor

Project description:We estimated differences of urethane-induced tumors between Nrf2+/+ and Nrf2-/- ICR mouse. To identify Nrf2-regulated genes in tumors, we examined the mRNA expression profile both in tumor and non-tumor tissue of mouse 4 months after urethane administration. We performed microarray analyses using the comparable size of lung tumors (1.0 mm < tumor diameter < 1.5 mm) and intact non-tumor lung tissues derived either from Nrf2+/+ (n=8) or Nrf2–/–mice (n=8) at 16-weeks after urethane(1-g/kg body weight) treatment.

2013-04-16 | E-GEOD-46048 | biostudies-arrayexpress

NQO1 protects obese mice through improvements in glucose and lipid metabolism.

Project description:Chronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes to energy metabolism regulation. Here, inducible activation of Nrf2 in mice and transgenesis of the Nrf2 target, NQO1, conferred protection from diet-induced metabolic defects through preservation of glucose homeostasis, insulin sensitivity, and lipid handling with improved physiological outcomes. NQO1-RNA interaction mediated the association with and inhibition of the translational machinery in skeletal muscle of NQO1 transgenic mice. NQO1-Tg mice on high-fat diet had lower adipose tissue macrophages and enhanced expression of lipogenic enzymes coincident with reduction in circulating and hepatic lipids. Metabolomics data revealed a systemic metabolic signature of improved glucose handling, cellular redox, and NAD<sup>+</sup> metabolism while label-free quantitative mass spectrometry in skeletal muscle uncovered a distinct diet- and genotype-dependent acetylation pattern of SIRT3 targets across the core of intermediary metabolism. Thus, under nutritional excess, NQO1 transgenesis preserves healthful benefits.

2024-05-23 | MTBLS2085 | MetaboLights

E-GEOD-52942

Project description:Comparison of gene expression profiles of anaplastic glioma with or without the mutated IDH1/2 gene

2015-08-25 | E-GEOD-52942 | ExpressionAtlas

Synergistic anti-tumor efficacy of mutant isocitrate dehydrogenase 1 inhibitor SYC-435 with standard therapy in patient-derived xenograft mouse models of glioma

Project description:Isocitrate dehydrogenase 1 (IDH1) is mutated in >70% of these tumors, making it an attractive therapeutic target. To determine the efficacy of our newly developed mutant IDH1 inhibitor, SYC-435 (1-hydroxypyridin-2-one), we treated orthotopic glioma xenograft model (IC-BT142AOA) carrying R132H mutation and our newly established orthotopic patient-derived xenograft (PDX) model of recurrent anaplastic oligoastrocytoma (IC-V0914AOA) bearing R132C mutation. In addition to suppressing IDH1 mutant cell proliferation in vitro, SYC-435 (15 mg/kg, daily x 28 days) synergistically prolonged animal survival times with standard therapies (Temozolomide + fractionated radiation) mediated by reduction of H3K4/H3K9 methylation and expression of mitochondrial DNA (mtDNA)-encoded molecules. Furthermore, RNA-seq of the remnant tumors identified genes (MYO1F, CTC1 and BCL9) and pathways (base excision repair, TCA cycle II, sirtuin signaling, protein kinase A, eukaryotic initiation factor 2 and α-adrenergic signaling) as mediators of therapy resistance.

2022-02-23 | GSE194169 | GEO

RNA-seq analysis of cymopol and algal extracts in the intestine

Project description:A natural product algal extract and its major component, cymopol, have demonstrated anti-oxidant and anti-inflammatory activity in vitro and in vivo. RNA transcript levels of Nqo1 and Hmox1 were discovered in multiple organs following oral gavage of 2 doses of the extract and cympopol for 3 consecutive days. The highest change in gene expression was noted in the digestive tract.

2017-12-03 | GSE107623 | GEO

Hepatic transcriptome analysis of WT and PRDX1Cys52Ser mutant mice on CDAHFD

Project description:In this study, we investigated how the peroxidase peroxiredoxin 1 protects against NASH. One previous study showed that PRDX1 cys52 was mutated to ser52 and consequently PRDX1’s peroxidase activity was impaired. Surprisingly, PRDX1Cys52Ser mice showed robust resistance to diet-induced NASH. To this end, We sought to understand how PRDX1Cys52Ser mutant confers resistance to NASH although impairing PRDX1’s peroxidase activity. We fed WT and PRDX1Cys52Ser mice a CDAHFD for 8 weeks and collected liver samples for RNA sequencing analysis. As revealed by gene-set enrichment analysis (GSEA) and KEGG pathway enrichment analysis, there was an enrichment of genes involved in inflammation, fiberosis and JAK-STAT signaling.

2024-12-05 | GSE271914 | GEO

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