41 research outputs found
Equation of state of argon : experiments on Z, density functional theory (DFT) simulations, and wide-range model.
Abstract Not Provide
Induction of Erythroid Differentiation in Human Erythroleukemia Cells by Depletion of Malic Enzyme 2
Malic enzyme 2 (ME2) is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and CO2 and uses NAD as a cofactor. Higher expression of this enzyme correlates with the degree of cell de-differentiation. We found that ME2 is expressed in K562 erythroleukemia cells, in which a number of agents have been found to induce differentiation either along the erythroid or the myeloid lineage. We found that knockdown of ME2 led to diminished proliferation of tumor cells and increased apoptosis in vitro. These findings were accompanied by differentiation of K562 cells along the erythroid lineage, as confirmed by staining for glycophorin A and hemoglobin production. ME2 knockdown also totally abolished growth of K562 cells in nude mice. Increased ROS levels, likely reflecting increased mitochondrial production, and a decreased NADPH/NADP+ ratio were noted but use of a free radical scavenger to decrease inhibition of ROS levels did not reverse the differentiation or apoptotic phenotype, suggesting that ROS production is not causally involved in the resultant phenotype. As might be expected, depletion of ME2 induced an increase in the NAD+/NADH ratio and ATP levels fell significantly. Inhibition of the malate-aspartate shuttle was insufficient to induce K562 differentiation. We also examined several intracellular signaling pathways and expression of transcription factors and intermediate filament proteins whose expression is known to be modulated during erythroid differentiation in K562 cells. We found that silencing of ME2 leads to phospho-ERK1/2 inhibition, phospho-AKT activation, increased GATA-1 expression and diminished vimentin expression. Metabolomic analysis, conducted to gain insight into intermediary metabolic pathways that ME2 knockdown might affect, showed that ME2 depletion resulted in high orotate levels, suggesting potential impairment of pyrimidine metabolism. Collectively our data point to ME2 as a potentially novel metabolic target for leukemia therapy
Recommended from our members
Equation of state of CO2 : experiments on Z, density functional theory (DFT) simulations, and tabular models.
The shock physics of giant impacts: Key requirements for the equations of state
We discuss major challenges in modeling giant impacts between planetary bodies, focusing on the equations of state (EOS). During the giant impact stage of planet formation, rocky planets are melted and partially vaporized. However, most EOS models fail to reproduce experimental constraints on the thermodynamic properties of the major minerals over the required phase space. Here, we present an updated version of the widely-used ANEOS model that includes a user-defined heat capacity limit in the thermal free energy term. Our revised model for forsterite (MgβSiOβ), a common proxy for the mantles of rocky planets, provides a better fit to material data over most of the phase space of giant impacts. We discuss the limitations of this model and the Tillotson equation of state, a commonly used alternative model
The shock physics of giant impacts: Key requirements for the equations of state
We discuss major challenges in modeling giant impacts between planetary
bodies, focusing on the equations of state (EOS). During the giant impact stage
of planet formation, rocky planets are melted and partially vaporized. However,
most EOS models fail to reproduce experimental constraints on the thermodynamic
properties of the major minerals over the required phase space. Here, we
present an updated version of the widely-used ANEOS model that includes a
user-defined heat capacity limit in the thermal free energy term. Our revised
model for forsterite (MgSiO), a common proxy for the mantles of rocky
planets, provides a better fit to material data over most of the phase space of
giant impacts. We discuss the limitations of this model and the Tillotson
equation of state, a commonly used alternative model.Comment: M-ANEOS source code public release
(https://github.com/isale-code/M-ANEOS); forsterite EOS public release
(https://github.com/ststewart/aneos-forsterite-2019); manuscript accepted (no
changes): Stewart, S., et al. (accepted). In J. Lane, T. Germann, and M.
Armstrong (Eds.), 21st Biennial APS Conference on Shock Compression of
Condensed Matter (SCCM19). AIP Publishin