To understand plant adaptation to heat stress, gene expression profiles of Arabidopsis leaves under heat stress, during recovery and control condition were obtained using microarray. Microarray data listed responsible candidate genes for glycerolipid metabolism.
Landscape of the lipidome and transcriptome under heat stress in Arabidopsis thaliana.
Age, Specimen part
View SamplesThe aim of this study is to investigate the gene expression profiles during masculinization of neonatal female mice brain by exogenous androgen treatment.
Gene expression profile of the neonatal female mouse brain after administration of testosterone propionate.
Sex, Specimen part, Treatment
View SamplesThe major antioxidant glutathione (GSH) protects cancer cells from oxidative damage leading to ferroptosis, an iron-dependent cell death. Therapy-resistant cancer cells often manifest high expression of the cystine-glutamate antiporter subunit xCT which enhances cystine uptake leading to GSH synthesis and thereby survive oxidative damage and ferroptosis. The use of GSH-depleting agents including xCT inhibitors might thus be expected to enhance the efficacy of cancer therapy. On the other hand, the efficacy of xCT-targeted therapy depends on the cellular metabolism affecting antioxidant system in cancer cells and metabolic reprograming might reduce the efficacy of cancer therapy using xCT inhibitors. Recently, to overcome the resistance to xCT-targeted therapy, we performed a library screening and identified an oral anesthetics dyclonine (DYC) as a sensitizing drug for xCT inhibitor sulfasalazine (SSZ). However, DYC is a local anesthetic and might not suitable for the systemic administration combined with SSZ in a clinical setting. In this study, we identified a vasodilator oxyfedrine (OXY) which is clinically used in systemic administration also acts as a sensitizing drug to GSH-depleting agents in multiple type of cancer cells. OXY and DYC share the motif required for the covalent inhibition of aldehyde dehydrogenases (ALDHs), and combined treatment with OXY and SSZ induced the accumulation of cytotoxic aldehyde 4-hydroxynonenal (4-HNE) and induce cell death in SSZ-resistant cancer cells. Furthermore, we found that OXY sensitizes cancer cells to radiation therapy which decreases intracellular GSH content. Our findings establish a rationale for repurposing of OXY as a sensitizing drug for xCT-targeted cancer therapy.
Vasodilator oxyfedrine inhibits aldehyde metabolism and thereby sensitizes cancer cells to xCT-targeted therapy.
Specimen part
View SamplesTo identify novel Peroxisome Proliferator-Activated Receptor gamma (PPARg) responsive secretory and/or transmembrane genes that is related to obesity, we integrated the expression data from the adipose tissue derived from obese mice with the other two data sets: expression profiling of adipocyte differentiation using ST2 cells and siRNA-mediated knockdown of Pparg during ST2 cell adipogenesis.
Fam57b (family with sequence similarity 57, member B), a novel peroxisome proliferator-activated receptor γ target gene that regulates adipogenesis through ceramide synthesis.
Specimen part
View SamplesPlants possess highly sensitive mechanisms that monitor environmental stress levels for a dose-dependent fine-tuning of their growth and development. Differences in plant responses to severe and mild abiotic stresses have been recognized. Although many studies have revealed that glutathione can contribute to plant tolerance to various environmental stresses, little is known about the relationship between glutathione and mild abiotic stress, especially the effect of stress-induced altered glutathione levels on the metabolism. Here, we applied a systems biology approach to identify key pathways involved in the gene-to-metabolite networks perturbed by low glutathione content under mild abiotic stress in Arabidopsis thaliana. We used glutathione synthesis mutants (cad2-1 and pad2-1) and plants overexpressing the gene encoding gamma-glutamylcysteine synthetase, the first enzyme of the glutathione biosynthetic pathway. The plants were exposed to two mild stress conditionsoxidative stress elicited by methyl viologen (MV) and stress induced by the limited availability of phosphate. We observed that the mutants and transgenic plants showed similar shoot growth as that of the wild-type plants under mild abiotic stress. We then selected the synthesis mutants and performed multi-platform metabolomics and microarray experiments to evaluate the possible effects on the overall metabolome and the transcriptome. To understand the metabolic responses observed under mild abiotic stress, we conducted gene expression profiling by Affymetrix ATH1 GeneChip. pad2-1 and the wild type Col-0 samples were harvested at 18 day-old after germination under two different stresses, MV treatment and limited phosphorus conditions.
Effects of Combined Low Glutathione with Mild Oxidative and Low Phosphorus Stress on the Metabolism of <i>Arabidopsis thaliana</i>.
Specimen part, Treatment
View SamplesWe explored Max ablation-mediated up-regulation of germ-related genes, especially meiosis-related genes in mouse embryonic stem cells which were cultured either under conventional mouse ES medium or 2i condition using inhibitors against MEK and GSK3b.
Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells.
Sex, Specimen part
View Samplesc-Myc is one of key players that are crucially involved in maintaining the undifferentiated state and the self-renewal of ESCs. To understand the mechanism by which c-Myc helps preserve these prominent characteristics of ESCs, we generated null-ES cells for the Max gene, which encodes the best characterized partner protein for all Myc family proteins. Although Myc/Max complexes have been widely regarded as crucial regulators of the ESC status, our data reveal that ESCs do not absolutely require these complexes in so-called ground state or related conditons and that this requirement is restricted to conventional ES culture conditions without using a MAPK inhibitor.
Indefinite self-renewal of ESCs through Myc/Max transcriptional complex-independent mechanisms.
Sex, Specimen part
View SamplesSphingomyelin synthase (SMS) 2 is the synthetic enzyme of sphingomyelin (SM), which regulates the fluidity and microdomain structure of the plasma membrane. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis, and found suppression of DSS-induced inflammation in SMS2 deficient (SMS2-/-) mice. Results provide insight into the role of SMS2 in inflammation.
Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer.
Specimen part
View SamplesBackground: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Methods: The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified eleven candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Results: Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. Conclusion: This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients.
Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer.
Specimen part
View Samples