Synthesis of N-chlorosulfonyl dicyclohexylamine as a potent inhibitor for spermidine synthase and its effects on human leukemia Molt4B cells

N-Chlorosulfonyl dicyclohexylamine (CSD) was synthesized as a potent inhibitor of spermidine synthase and analyzed for antiproliferative effects on leukemic cells. The compound specifically inhibited spermidine synthase in a competitive mode with the substrate putrescine (Ki, 1.8 X 10(-7) M). When human leukemia Molt4B cells were cultured in the presence of the inhibitor, the intracellular level of spermidine and the rate of cell proliferation were markedly depressed. In these polyamine depleted and growth retarded cells the synthesis of protein, but not of DNA or RNA, was found to be significantly diminished.     

Shear Stress-induced Redistribution of Vascular Endothelial-Protein-tyrosine Phosphatase (VE-PTP) in Endothelial Cells and Its Role in Cell Elongation

Vascular endothelial cells (ECs) are continuously exposed to shear stress (SS) generated by blood flow. Such stress plays a key role in regulation of various aspects of EC function including cell proliferation and motility as well as changes in cell morphology. Vascular endothelial-protein-tyrosine phosphatase (VE-PTP) is an R3-subtype PTP that possesses multiple fibronectin type III-like domains in its extracellular region and is expressed specifically in ECs. The role of VE-PTP in EC responses to SS has remained unknown, however. Here we show that VE-PTP is diffusely localized in ECs maintained under static culture conditions, whereas it undergoes rapid accumulation at the downstream edge of the cells relative to the direction of flow in response to SS. This redistribution of VE-PTP triggered by SS was found to require its extracellular and transmembrane regions and was promoted by integrin engagement of extracellular matrix ligands. Inhibition of actin polymerization or of Cdc42, Rab5, or Arf6 activities attenuated the SS-induced redistribution of VE-PTP. VE-PTP also underwent endocytosis in the static and SS conditions. SS induced the polarized distribution of internalized VE-PTP. Such an effect was promoted by integrin engagement of fibronectin but prevented by inhibition of Cdc42 activity or of actin polymerization. In addition, depletion of VE-PTP by RNA interference in human umbilical vein ECs blocked cell elongation in the direction of flow induced by SS. Our results suggest that the polarized redistribution of VE-PTP in response to SS plays an important role in the regulation of EC function by blood flow.     

Influence of Dietary Condition on Muscle Protein Composition

Contents of arginine, methionine, histidine, phenylalanine, tryptophan and tyrosine were measured in the “Extract” and the “Fibrous” proteins obtained by urea fractionation from the skeletal muscle of rats fed a normal, a tryptophan-free and a protein-free diets for 30 days respectively. The ratios of the “Extract” to the “Fibrous” proteins were remarkably different in the muscles of the different dietary groups. Significant differences, were observed in the amino acid compositions of the protein fractions between the normal and both deficient groups showing the presence of the different dietary effects on the constituent proteins of the muscle.

A quantitative fractionation method of muscle protein was presented. Muscles from the adult rats fed a normal, a tryptophan-free and a protein-free diets separately for 4 weeks were fractionated by this method. The effects on the composition of the muscle protein fractions were different between the tryptophan-free and the protein-free diets. The decreases of non-protein nitrogen and sarcoplasmic protein by both deficient diets were greater than that of total muscle nitrogen, whereas those of actin, myosin and stroma were smaller. This shows the presence of the different dietary effects on the constituent proteins of muscle.     

Novel lipase-catalyzed ring-opening copolymerization of lactide and trimethylene carbonate forming poly(ester carbonate)s.

Poly(lactide-co-trimethylene carbonate)s were prepared by the lipase-catalyzed ring-opening copolymerization of lactide and trimethylene carbonate having carbonate content from 0 to 100%. Their thermal properties and enzymatic degradability were measured. The L,L-, D,D- and D,L-lactides were copolymerized with trimethylene carbonate by porcine pancreatic lipase to produce random copolymers having molecular weights of up to 21000. The glass transition temperature (Tg of the copolymer was dependent on the carbonate content and the Tg values linearly decreased from 35 degrees C (polylactide) to -8 degrees C [poly(trimethylene carbonate)]. Among the lipases tested, the porcine pancreatic lipase and proteinase K showed biodegradability towards poly(ester-carbonate)s.     

Age-Associated Different Transcriptome Profiling in Zebrafish and Rats: an Insight into the Diversity of Vertebrate Aging

Marine Biotechnology - Most mammals, including humans, show obvious aging phenotypes, for example, loss of tissue plasticity and sarcopenia. In this regard, fish can be attractive models to study...     

The Suppression of Maternal–Fetal Leukemia Inhibitory Factor Signal Relay Pathway by Maternal Immune Activation Impairs Brain Development in Mice

Recent studies in rodents suggest that maternal immune activation (MIA) by viral infection is associated with schizophrenia and autism in offspring. Although maternal IL-6 is though t to be a possible mediator relating MIA induced these neuropsychiatric disorders, the mechanism remains to be elucidated. Previously, we reported that the maternal leukemia inhibitory factor (LIF)–placental ACTH–fetal LIF signaling relay pathway (maternal–fetal LIF signal relay) promotes neurogenesis of fetal cerebrum in rats. Here we report that the maternal–fetal LIF signal relay in mice is suppressed by injection of polyriboinosinic-polyribocytidylic acid into dams, which induces MIA at 12.5 days post-coitum. Maternal IL-6 levels and gene expression of placental suppressor of cytokine signaling 3 (Socs3) increased according to the severity of MIA and gene expression of placental Socs3 correlated with maternal IL-6 levels. Furthermore, we show that MIA causes reduction of LIF level in the fetal cerebrospinal fluid, resulting in the decreased neurogenesis in the cerebrum. These findings suggest that maternal IL-6 interferes the maternal–fetal LIF signal relay by inducing SOCS3 in the placenta and leads to decreased neurogenesis.