Thapsigargin suppresses alpha 1-acid glycoprotein secretion independently of N-glycosylation and ER stress.

Alpha-1 acid glycoprotein (AGP) is a major acute-phase protein that is involved in drug/ligand binding and regulation of immune response. In response to inflammation, AGP secretion from the liver increases, resulting in elevated concentration of plasma AGP. AGP exhibits multiple N-glycosylation sites, and thus, is highly glycosylated. Although AGP glycosylation is considered to affect its functions, the significance of AGP glycosylation for its secretion is unclear. In this study, we investigated the effects of AGP glycosylation using glycosylation-deficient mouse AGP mutants lacking one, four, or all five N-glycosylation sites. Furthermore, we examined the effects of endoplasmic reticulum (ER) stress-inducing reagents, including tunicamycin and thapsigargin, which induce ER stress in an N-glycosylation-dependent and -independent manner, respectively. Here, we found that glycosylation deficiency and ER stress induce a little or no effect on AGP secretion. Conversely, thapsigargin significantly suppressed AGP secretion in glycosylation-independent manner. These findings indicate that AGP secretion is regulated via thapsigargin-sensitive pathway that might be further controlled by the intracellular calcium concentrations.

Effect of AlGaN undershell on the cathodoluminescence properties of coaxial GaInN/GaN multiple-quantum-shells nanowires.

Coaxial GaInN/GaN multiple-quantum-shells (MQSs) nanowires (NWs) were grown on an n-type GaN/sapphire template employing selective growth by metal-organic chemical vapour deposition (MOCVD). To improve the cathodoluminescence (CL) emission intensity, an AlGaN shell was grown underneath the MQS active structures. By controlling the growth temperature and duration, an impressive and up to 11-fold enhancement of CL intensity is achieved at the top area of the GaInN/GaN MQS NWs. The spatial distribution of Al composition in the AlGaN undershell was assessed as a function of position along the NW and analysed by energy-dispersive X-ray measurement and CL characterisation. By introducing an AlGaN shell underneath GaInN/GaN MQS, the diffusion of point defects from the n-core to MQS is effectively suppressed because of the lower formation energy of vacancies-complexes in AlGaN in comparison to GaN. Moreover, the spatial distribution of Al and In was attributed to the insufficient delivery of gas precursors to the bottom of the NWs and the anisotropy diffusion on the nonpolar m-planes. This investigation can shed light on the effect of the AlGaN undershell on improving the emission efficiency of NW-based white and micro-light-emitting diodes (LEDs).

Amino acid starvation accelerates replication of Ibaraki virus.

Ibaraki virus (IBAV) is a strain of epizootic hemorrhagic disease virus 2 that belongs to the genus Orbivirus of the family Reoviridae. IBAV replication is suppressed by the inhibition of autophagy, and since mechanistic target of rapamycin complex 1 (mTORC1) is a key regulator of autophagy, we examined if mTORC1 inhibition by amino acid starvation or mTOR inhibitors (Torin 1 and rapamycin) affects IBAV replication. We found that IBAV replication is significantly enhanced after amino acid starvation of host cells, but not after treatment with mTOR inhibitors, during early stages of viral infection (0-1 hpi). Notably, inhibition of mTORC1 by amino acid starvation was reversible and thus restricted to 0-1 hpi, whereas mTOR inhibitors sustainably suppressed mTORC1 even after the 1-h treatment, suggesting that mTORC1 suppression itself does not affect IBAV replication. To investigate the mechanism of enhanced IBAV replication by amino acid starvation, we examined the endocytic pathway, since IBAV utilizes acidification of endosomes as a trigger for viral replication. Accordingly, we found that amino acid starvation, but not mTOR inhibitors, strongly induced acidification of endosomes/lysosomes and that inhibition of endosomal acidification by bafilomycin A1 effectively blocked enhancement of IBAV replication. Altogether, the inactivation of mTORC1 by amino acid starvation during early stages of infection enhances acidification of endosomes, which in turn enhances IBAV replication.