In this study, we have used a combination of transcriptomics and proteomics technologies to investigate the response of human hepatoma PLC/PRF/5 cells to prohibitin silencing to define in detail the biological function of hepatic Phb1 and to elucidate potential prohibitin-dependent mechanisms participating in the maintenance of the transformed phenotype. Abrogation of prohibitin reduced proliferation and induced apoptosis in human hepatoma cells in a mechanism dependent on NF kappa B signaling. Moreover, down-regulation of ERp29 together with down-regulation of Erlin 2 suggests ER stress. In agreement, increased C/EBP homologous protein levels, poly-ADP ribose polymerase cleavage

and activation of caspase 12 and downstream caspase 7 evidenced ER stress-induced apoptosis. Down-regulation of Selisistat manufacturer CFTRinh-172 purchase proteasome activator complex subunit 2 and stathmin as well as accumulation of ubiquitinated proteins suggest interplay between ER stress and proteasome malfunction. Taken together, our results provide evidences for prohibitin having a central role in the maintenance

of the transformed and invasive phenotype of human hepatoma cells and may further support previous studies suggesting prohibitin as a potential clinical target.”
“Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are leading causes of morbidity and mortality in the elderly. Both diseases are characterized by amyloid deposition in target tissues: aggregation of amylin in T2DM is associated with loss of insulin-secreting beta-cells, while amyloid beta (A beta) aggregation in AD brain is associated with neuronal loss. Here, we used quantitative iTRAQ proteomics as a discovery tool to show that both All and human amylin (HA) deregulate identical proteins, a quarter of which https://www.selleck.cn/products/NVP-AUY922.html are mitochondria], supporting the notion that mitochondrial dysfunction is a common target in these two amyloidoses. A functional validation revealed that

mitochondrial complex IV activity was significantly reduced after treatment with either HA or A beta, as was mitochondria] respiration. In comparison, complex I activity was reduced only after treatment with HA. A beta and HA, but not the non-amyloidogenic rat amylin, induced significant increases in the generation of ROS. Co-incubation of HA and A beta did not produce an augmented effect in ROS production, again suggesting common toxicity mechanisms. In conclusion, our data suggest that A[3 and HA both exert toxicity, at least in part, via mitochondrial dysfunction, thus restoring their function may be beneficial for both AD and T2DM.”
“Sequencing of at least 13 Staphylococcus aureus isolates has shown that genomic plasticity impacts significantly on the repertoire of virulence factors. However, genome sequencing does not reveal which genes are expressed by individual isolates. Here, we have therefore performed a comprehensive survey of the composition and variability of the S. aureus exoproteome.