For this purpose, 10 months aged mice were fed for 3 months on food pellets contained 1 g (L1 group) or 2 g (L2 group) lithium carbonate/kg, resulting in serum concentrations of 0.4 and 0.8 mM, respectively. The evaluation of lipid peroxidation level and the activities of catalase, superoxide-dismutase P5091 mw and glutathione-peroxidase showed that chronic Li administration, at therapeutic doses doesn’t induce oxidative stress

in brain tissue. No changes in the expression levels of molecular chaperones, namely, the HSP70, and HSP90 heat shock proteins and the GRP94 glucose-regulated protein were detected. Moreover, this treatment has caused (1) an increase in the relative brain weight (2) a delay in the age induced cerebral glucose impairment (3) an enhancement of the neurogenesis in hippocampus and enthorinal cortex highlighted by silver impregnation. Under these experimental conditions, no modifications were observed in expression levels of GSK3 and of its downstream target beta-catenin proteins. These results suggested that chronic Li administration, at therapeutic doses, has a neuroprotective/neurotrophic properties and its therapeutic Dorsomorphin mechanism doesn’t implicate GSK3 inactivation.”
“Camptothecin (CPT), a topoisomerase (Top) I-targeting drug that stabilizes Top1-DNA covalent

adducts, can induce S-phase-specific cytotoxicity due to the arrest of progressing replication forks. However, CPT-induced non-S-phase cytotoxicity is less well characterized. In this study, we have identified topoisomerase II beta (Top2 beta) as a specific determinant for CPT sensitivity, but not for many other cytotoxic agents, in non-S-phase cells. First, quiescent mouse embryonic fibroblasts (MEFs) lacking Top2 beta were shown to be hypersensitive to CPT with prominent induction of apoptosis. Second, ICRF-187, a Top2 catalytic inhibitor known to deplete Top2 beta, specifically sensitized MEFs to CPT. To explore SBE-β-CD molecular weight the molecular basis for CPT hypersensitivity in Top2 beta-deficient cells, we found that upon CPT exposure, the RNA polymerase II large subunit (RNAP LS) became

progressively depleted, followed by recovery to nearly the original level in wild-type MEFs, whereas RNAP LS remained depleted without recovery in Top2 beta-deficient cells. Concomitant with the reduction of the RNAP LS level, the p53 protein level was greatly induced. Interestingly, RNAPLS depletion has been well documented to lead to p53-dependent apoptosis. Altogether, our findings support a model in which Top2 beta deficiency promotes CPT-induced apoptosis in quiescent non-S-phase cells, possibly due to RNAP LS depletion and p53 accumulation.”
“gamma-Butyrolactones 4a1, 4a2, 4b1 and 4b2 were carefully studied through NMR experiments. H-1 NMR, C-13 H-1 NMR, COSY, HMQC, HMBC and J-res experiments were performed to provide the needed structure information.