The second messenger cAMP acts via protein kinase A (PKA) to induce apoptosis by mechanisms that are poorly understood. Here, we assessed a role for mitochondria and analyzed gene expression in cAMP/PKA-promoted apoptosis by comparing wild-type (WT) S49 lymphoma cells and the S49 variant, D- (cAMP-deathless), which lacks cAMP-promoted apoptosis but has wild-type levels of PKA activity and cAMP-promoted G1 growth arrest. Treatment of WT, but not D-, S49 cells with 8-CPT-cAMP for 24 h induced loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and Smac and increase in caspase-3 activity. Gene expression analysis (using Affymetrix 430 2.0 Arrays) revealed that WT and D- cells incubated with 8-CPT-cAMP have similar, but non-identical, extents of cAMP-regulated gene expression at 2h (~800 transcripts) and 6h (~1000 transcripts) (|Fold|>2, P<0.06); by contrast, at 24h ~2500 and ~1100 transcripts were changed in WT and D- cells, respectively. Using an approach that combined regression analysis, clustering and functional annotation to identify transcripts that showed differential expression between WT and D- cells, we found differences in cAMP-mediated regulation of mRNAs involved in transcriptional repression, apoptosis, the cell cycle, RNA splicing, Golgi and lysosomes. The 2 cell lines differed in CREB phosphorylation and expression of the transcriptional inhibitor Icer and in cAMP-regulated expression of genes in the Inhibitor of apoptosis (IAP) and Bcl families. The findings indicate that cAMP/PKA-promoted apoptosis of lymphoid cells occurs via mitochondrial-mediated events and imply that such apoptosis involves gene networks in multiple biochemical pathways.
Gene expression signatures of cAMP/protein kinase A (PKA)-promoted, mitochondrial-dependent apoptosis. Comparative analysis of wild-type and cAMP-deathless S49 lymphoma cells.
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View SamplesAbstract
Gene expression patterns define key transcriptional events in cell-cycle regulation by cAMP and protein kinase A.
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View SamplesTo address the mechanisms of suppression, we analyzed time course of mRNA expression of four suppressed smc2-8 mutant strains.
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Specimen part, Time
View SamplesAge-dependent electrical and morphological remodeling of the Drosophila heart caused by hERG/seizure mutations
Age-dependent electrical and morphological remodeling of the Drosophila heart caused by hERG/seizure mutations.
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View SamplesFour healthy human volunteers underwent an acute bout of resistance exercise with the right leg at 2 pm. Biopsies were removed from the Vastus Lateralis muscle 6 h (8 pm) and 18 h (8 am) after exericise
Time- and exercise-dependent gene regulation in human skeletal muscle.
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View SamplesHeart performance declines with age. Reduced protein quality control (PQC) due to decreased function of the ubiquitin/proteasome system (UPS), autophagy, and/or chaperone-mediated protein refolding is a likely contributor to age-associated cardiac performance decline. The transcription factor FOXO participates in the regulation of genes involved PQC and a host of other processes. Here, the effect of cardiac-restricted dFOXO overexpression was investigated in Drosophila, a genetically pliable and rapidly aging model. Modest dFOXO overexpression in the heart was protective, ameliorating functional decline with age. Increased expression of genes associated predominantly with UPS relative to other PQC components accompanied dFOXO-mediated cardioprotection, which was corroborated by a significant decrease in ubiquitinated myocardial proteins.
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Specimen part
View SamplesAmplificaition of HOXD9 and HOXD13 genes was found in MWCNTs induced carcinogencity. By overexpression or silence of of HOXD9 and HOXD13 gene may alter tumorigenicity.
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Cell line
View Samplescompare the RNA-seq profile with the original
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View SamplesRNS-seq
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View SamplesThe induced pluripotent stem-like cells from human gastric cell line, KMU-CS12 (CS12) were derived from putative human gastric stem cell/progenitor cell clone. CS12 expressed cancer cell phenotypes, i.e. the ability of anchorage-independent growth high frequency (44%) and to the expression of Oct4, a stemness marker and many types of cancer cells, and tumor development in immune deficient mice.
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