Whole genome expression profiling in the presence and absence of annexin A2 [shRNA] identified fundamentally altered transcriptional programming that changes the radioresponsive transcriptome.
Annexin A2 modulates radiation-sensitive transcriptional programming and cell fate.
Treatment, Time
View SamplesStudies were undertaken to determine whether oscillatory behavior in the extracellular signal regulated kinase (ERK) pathway results in unique gene regulation patterns. Microarray analysis was performed on three subcloned populations of human keratinocytes with distinct ERK signaling/oscillation phenotypes.
ERK oscillation-dependent gene expression patterns and deregulation by stress response.
Specimen part
View SamplesOsteocytes, positioned within bones interstitial space, are subject to fluid flow upon whole bone loading. Such fluid flow is widely theorized to be a mechanical signal transduced by osteocytes, initiating a poorly understood cascade of signaling events mediating bone metabolism. The objective of this study was to utilize high-throughput approaches to examine the time course of flow-induced changes in osteocyte gene transcript and protein levels.
No associated publication
Specimen part, Treatment, Time
View SamplesUsing a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.
Macrophage responses to silica nanoparticles are highly conserved across particle sizes.
No sample metadata fields
View SamplesWe have investigated the regulation of anchorage-independent growth (AIG) by basic fibroblast growth factor (bFGF) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) in JB6 mouse epidermal cells in the context of wound repair versus carcinogenesis responses. bFGF induces an unusually efficient but reversible AIG response, relative to TPA-induced AIG which is irreversible. Distinct global gene expression profiles are associated with anchorage-independent colonies arising from bFGF-stimulated JB6 cells, relative to colonies arising from fully tumorigenic JB6 cells (RT101), including genes exhibiting reciprocal regulation patterns. Thus, while TPA exposure results in commitment to an irreversible and tumorigenic AIG phenotype, the AIG response to bFGF is reversible with essentially complete restoration of normal cell cycle check point control following removal of bFGF from growth medium. These results are consistent with the physiological role of bFGF in promoting wound healing, and suggest that natural mechanisms exist to reverse transformative cellular phenotypes associated with carcinogenesis.
Cellular dichotomy between anchorage-independent growth responses to bFGF and TPA reflects molecular switch in commitment to carcinogenesis.
No sample metadata fields
View SamplesHere we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation.
Hepatic leukemia factor promotes resistance to cell death: implications for therapeutics and chronotherapy.
Cell line
View SamplesNeural tube defects (NTDs) are serious birth defects with an estimated worldwide incidence of 1 per 1,000 live births. The multifactorial nature of NTDs in humans has made it difficult to elucidate pathogenesis mechanisms. However, a strong relationship has been established between folate-homocysteine metabolism and NTD risk. Prevention of a substantial proportion of fetal NTDs can be achieved through maternal folic acid (FA) supplementation. However the mechanism by which FA exerts its beneficial effect remains unclear. METHODS: To improve our understanding of the underlying mechanisms of NTD pathogenesis and the ways in which folate exerts its beneficial effect, we analyzed mRNA profiles as well as folate and vitamin B12 levels in five NTD mouse mutants whose response to dietary FA was previously established. RESULTS: Differentially expressed genes representing the effect of each NTD-causing mutation were identified and associated with biologic pathways. Interestingly, the panel of NTD mutants collectively revealed pathways related to two nuclear receptors, retinoid X receptor (RXR) and pregnane X receptor (PXR), suggesting that these pathways may be related to a shared mechanism of NTD development. Moreover, the NTD-causing mutations that were associated with FA responsiveness had expression profiles that were related to folate-homocysteine metabolic pathways. These pathways were not strongly associated with mutants that do not respond to FA supplementation, implying that FA may be beneficial when the NTD mutation affects pathways related to folate-homocysteine metabolism.
No associated publication
Sex, Specimen part
View SamplesParaquat and diquat are viologen herbicides used in commercial agriculture and for residential outdoor weed control. They are related structurally, each containing multiple aromatic rings and two quaternary ammonium cations. Paraquat is one of the most widely used herbicides in the world; however, due to recent toxicity studies and its association with Parkinson’s disease, it is now available only to commercially licensed users in the United States. In contrast, diquat has not been associated with Parkinson’s disease and is available for both commercial and residential applications in the United States. In general, the proposed mechanism by which toxicity occurs following exposure to either herbicide is similar. Both are readily converted to free radicals via the superoxide anion radical and react with molecular oxygen to generate additional redox products that promote oxidative stress and potentially cell death. Diquat is generally considered a safer alternative to paraquat based on its lower incidence of poisoning reports; however, recent work in our lab suggests diquat is significantly more hepatotoxic than paraquat. Studies reporting direct comparisons of paraquat and diquat, especially regarding their potential impact on liver injury, are definitely lacking. The goal of this project is to address this knowledge gap by exposing an in vitro hepatocellular model (TGF-alpha transgenic mouse hepatocytes; TAMH) with each viologen herbicide to further elucidate toxicologic mechanisms and outcomes. The microarray data identified MAPK as an important contributor to diquat-induced toxicity and offers a new generalized approach for broader gene expression-level investigations.
No associated publication
Cell line
View SamplesWe carried out a global whole blood genome wide expression profiling of HIV exposed and uninfected women from Nairobi to identify host factors which may be a key contribution to HIV resistance phenomenon.
Microarray analysis of HIV resistant female sex workers reveal a gene expression signature pattern reminiscent of a lowered immune activation state.
Specimen part
View SamplesPlasma membrane NADPH oxidases (NOXs) are major producers of reactive oxygen species (ROS) in plant cells under normal growth and stress conditions. Rice NOXs have multiple homologs but their functional mechanisms are largely unknown.
The plasma membrane NADPH oxidase OsRbohA plays a crucial role in developmental regulation and drought-stress response in rice.
Specimen part, Treatment
View Samples