Merlin/NF2 regulates SLC7A11/xCT expression and cell viability under glucose deprivation at high cell density in glioblastoma cells.

The cystine/glutamate transporter SLC7A11/xCT is highly expressed in many cancer cells and plays an important role in antioxidant activity by supplying cysteine for glutathione synthesis. Under glucose-depleted conditions, however, SLC7A11-mediated cystine uptake causes oxidative stress and cell death called disulfidptosis, a new form of cell death. We previously reported that high cell density (HD) promotes lysosomal degradation of SLC7A11 in glioblastoma cells, allowing them to survive under glucose-depleted conditions. In this study, we found that the neurofibromatosis type 2 gene, Merlin/NF2 is a key regulator of SLC7A11 in glioblastoma cells at HD. Deletion of Merlin increased SLC7A11 protein level and cystine uptake at HD, leading to promotion of cell death under glucose deprivation. Furthermore, HD significantly decreased SLC7A11 mRNA level, which was restored by Merlin deletion. This study suggests that Merlin suppresses glucose deprivation-induced cell death by downregulating SLC7A11 expression in glioblastoma cells at HD.

Pyridine-mediated B-B bond cleavage of tetrahydroxydiboron to synthesize n-doped SWCNTs with long-term air stability.

Neutral radicals, including carbon radicals, are highly useful chemical species for the functionalization of semiconducting materials to change their electrical and optical properties owing to their high reactivity. However, boron radicals have been limited to synthetic and reaction chemistry, with rare utilization in materials science. In this study, a mixture of tetrahydroxydiboron (B2(OH)4) and pyridine derivatives was found to act as an electron dopant for single-walled carbon nanotubes (SWCNTs) because of the electron transfer from pyridine-mediated boron radicals generated by B-B bond dissociation to neutral radicals. In particular, the radical formed from a mixture of B2(OH)4 and 4-phenylpyridine ((4-Phpy)B(OH)2·) efficiently doped electrons into the SWCNT films; thus, n-type SWCNTs with long-term air stability for more than 50 days at room temperature were prepared. Furthermore, the experimental and theoretical surface analyses revealed that the formation of stable cations from ((4-Phpy)B(OH)2·) and the efficient interaction with SWCNTs due to their high planarity served as the mechanism for their stable doping.

Fine microstructure formation in steel under ultrafast heating and cooling.

This study evaluates phase transformation kinetics under ultrafast cooling using femtosecond X-ray diffraction for the operand measurements of the dislocation densities in Fe-0.1 mass% C-2.0 mass% Mn martensitic steel. To identify the phase transformation mechanism from austenite (γ) to martensite (α'), we used an X-ray free-electron laser and ultrafast heating and cooling techniques. A maximum cooling rate of 4.0 × 103 °C s-1 was achieved using a gas spraying technique, which is applied immediately after ultrafast heating of the sample to 1200 °C at a rate of 1.2 × 104 °C s-1. The cooling rate was sufficient to avoid bainitic transformation, and the transformation during ultrafast cooling was successfully observed. Our results showed that the cooling rate affected the dislocation density of the γ phase at high temperatures, resulting in the formation of a retained γ owing to ultrafast cooling. It was discovered that Fe-0.1 mass% C-2.0 mass% Mn martensitic steels may be in an intermediate phase during the phase transformation from face-centered-cubic γ to body-centered-cubic α' during ultrafast cooling and that lattice softening occurred in carbon steel immediately above the martensitic-transformation starting temperature. These findings will be beneficial in the study, development, and industrial utilization of functional steels.

High cell density increases glioblastoma cell viability under glucose deprivation via degradation of the cystine/glutamate transporter xCT (SLC7A11).

The cystine/glutamate transporter system xc- consists of the light-chain subunit xCT (SLC7A11) and the heavy-chain subunit CD98 (4F2hc or SLC3A2) and exchanges extracellular cystine for intracellular glutamate at the plasma membrane. The imported cystine is reduced to cysteine and used for synthesis of GSH, one of the most important antioxidants in cancer cells. Because cancer cells have increased levels of reactive oxygen species, xCT, responsible for cystine-glutamate exchange, is overexpressed in many cancers, including glioblastoma. However, under glucose-limited conditions, xCT overexpression induces reactive oxygen species accumulation and cell death. Here we report that cell survival under glucose deprivation depends on cell density. We found that high cell density (HD) down-regulates xCT levels and increases cell viability under glucose deprivation. We also found that growth of glioblastoma cells at HD inactivates mTOR and that treatment of cells grown at low density with the mTOR inhibitor Torin 1 down-regulates xCT and inhibits glucose deprivation-induced cell death. The lysosome inhibitor bafilomycin A1 suppressed xCT down-regulation in HD-cultured glioblastoma cells and in Torin 1-treated cells grown at low density. Additionally, bafilomycin A1 exposure or ectopic xCT expression restored glucose deprivation-induced cell death at HD. These results suggest that HD inactivates mTOR and promotes lysosomal degradation of xCT, leading to improved glioblastoma cell viability under glucose-limited conditions. Our findings provide evidence that control of xCT protein expression via lysosomal degradation is an important mechanism for metabolic adaptation in glioblastoma cells.