It is well appreciated that reactive oxygen species (ROS) are deleterious to mammals, including humans, especially when generated in abnormally large quantities from cellular metabolism. Whereas the mechanisms leading to the production of ROS are rather well delineated, the mechanisms underlying tissue susceptibility or tolerance to oxidant stress remain elusive. Through an experimental selection over many generations, we have previously generated Drosophila melanogaster flies that tolerate tremendous oxidant stress and have shown that the family of antimicrobial peptides (AMP) is over-represented in these tolerant flies. Furthermore, we have also demonstrated that overexpression of even one AMP at a time (e.g. Diptericin) allows wild type flies to survive much better in hyperoxia. In the current study, we used a number of experimental approaches to investigate the potential mechanisms underlying hyperoxia tolerance in flies with antimicrobial peptide overexpression. We demonstrate that flies with Diptericin overexpression resist oxidative stress by increasing antioxidant enzyme activities and preventing an increase in ROS level after hyperoxia. Depleting the GSH pool using buthionine sulfoximine limits fly survival, thus confirming that enhanced survival observed in these flies is related to improved redox homeostasis. We conclude that a) AMPs play an important role in tolerance to oxidant stress; b) overexpression of Diptericin changes the cellular redox balance between oxidant and antioxidant, and c) this change in redox balance plays an important role in survival in hyperoxia.
Antimicrobial peptides increase tolerance to oxidant stress in Drosophila melanogaster.
Specimen part
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Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults.
Sex, Specimen part
View SamplesWe tested the hypothesis on the mechanisms responsible for the early control of NK cell function by identifying a discrete set of genes in circulating NK cells that were altered by exercise.
Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults.
Sex, Specimen part
View SamplesWe tested the hypothesis on the mechanisms responsible for the early control of monocytes function by identifying a discrete set of genes in circulating monocytes that were altered by exercise.
Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.
Sex, Specimen part, Time
View SamplesOne of the critical substances that mammals highly regulate via the respiratory, cardiovascular and neurologic systems is O2. Both low and high O2 levels can induce major morbidities as well as mortality. Indeed, O2 has been often considered as both an elixir and a poison in humans. In current study, we have used an experimental selection approach to generate Drosophila strains that are tolerant to severe hyperoxic environment. Gene expression profiling is then applied to investigate the mechanisms underlying hyperoxia tolerance in the newly generated strains.
Experimental selection for Drosophila survival in extremely high O2 environments.
Specimen part
View SamplesBackground: Constant hypoxia (CH) and intermittent hypoxia (IH) occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s) in D. melanogaster after exposure to severe (1% O2) intermittent or constant hypoxia.
Distinct mechanisms underlying tolerance to intermittent and constant hypoxia in Drosophila melanogaster.
Specimen part
View SamplesHypoxia plays a key pathogenic role in the outcome of many pathologic conditions. To elucidate how organisms successfully adapt to hypoxia, a population of Drosophila melanogaster was generated, through an iterative selection process, that is able to complete its lifecycle at 4% O2, a level lethal to the starting parental population. Transcriptomic analysis of flies adapted for >200 generations was performed to identify pathways and processes that contribute to the adapted phenotype, comparing gene expression of three developmental stages with generation-matched control flies. A third group was included, hypoxia-adapted flies reverted to 21% O2 for five generations, to address the relative contributions of genetics and hypoxic environment to the gene expression differences. We identified the largest number of expression differences in 0.5-3 hr post-eclosion adult flies that were hypoxia-adapted and maintained in 4% O2, and found evidence that changes in Wnt signaling contribute to hypoxia tolerance in flies.
Wnt pathway activation increases hypoxia tolerance during development.
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View SamplesUsing long-oligo beadschip arrays, we examined the global gene expression profile in cultured hippocampal slices under the simulated ischemic condition with and without the presence of DIDS .
DIDS protects against neuronal injury by blocking Toll-like receptor 2 activated-mechanisms.
Sex, Specimen part
View SamplesStem cells are a potential key strategy for treating neurodegenerative diseases in which the generation of new neurons is critical. A better understanding of the characteristics and molecular properties of neural stem cells (NSC) and differentiated neurons can help in assessing neuronal maturity and possibly in devising better therapeutic strategies. We have therefore performed an in-depth gene expression profiling study of the C17.2 NSC line and primary neurons (PN) derived from embryonic mouse brains. Microarray analysis revealed a neuron-specific gene expression signature that distinguishes PN from NSCs, with elevated levels of transcripts involved in neuronal functions such as neurite development, axon guidance, in PN. The same comparison revealed decreased levels of multiple cytokine transcripts such as IFN, TNF, TGF, and IL. Among the differentially expressed genes, we found a statistically significant enrichment of genes in the ephrin, neurotrophin, CDK5 and actin pathways which control multiple neuronal-specific functions. Furthermore, genes involved in cell cycle were among the most significantly changed in PN. In order to better understand the role of cell cycle arrest in mediating NSCs differentiation, we blocked the cell cycle of NSCs with Mitomycin C (MMC) and examined cellular morphology and gene expression signatures. Although these MMC-treated NSCs displayed a neuronal morphology and expressed some neuronal differentiation marker genes, their gene expression patterns was very different from primary neurons. We conclude that: 1) Fully differentiated primary neurons display a specific neuronal gene expression signature; 2) cell-cycle block in NSC does not induce the formation of fully differentiated neurons; 3) Cytokines such as IFN, TNF, TGF and IL are part of normal NSC function and/or physiology; 4) Signaling pathways of ephrin, neurotrophin, CDK5 and actin, related to major neuronal features, are dynamically enriched in genes showing changes in expression level.
Identification of a neuronal gene expression signature: role of cell cycle arrest in murine neuronal differentiation in vitro.
Sex, Specimen part, Cell line
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