Facile acylation of α-chitin in ionic liquid.

Based on the fact that an ionic liquid, 1-allyl-3-methylimidazolium bromide (AMIMBr), efficiently dissolved α-chitin, this study investigated the development of facile acylation reactions of α-chitin in AMIMBr media. Under optimal conditions in the presence of pyridine and N,N-dimethyl-4-aminopyridine as base and catalyst, respectively, lauroylation of α-chitin smoothly took place using lauroyl chloride in AMIMBr at 100 °C for 24 h to produce a chitin laurate with a high degree of substitution (DS). Chitin acylates having different substituents were also synthesized by acylation of α-chitin using various acyl chlorides under the same conditions. In addition to IR analysis of the products, 1H NMR measurement was allowed for structure confirmation owing to the dissolution of the high DS derivatives in CDCl3/CF3CO2H mixed solvents.

Membrane microdomain-associated uroplakin IIIa contributes to Src-dependent mechanisms of anti-apoptotic proliferation in human bladder carcinoma cells.

Our previous study demonstrated that tyrosine phosphorylation of p145(met)/ß-subunit of hepatocyte growth factor receptor by epidermal growth factor receptor and Src contributes to the anti-apoptotic growth of human bladder carcinoma cell 5637 under serum-starved conditions. Here, we show that some other cell lines of human bladder carcinoma, but not other types of human cancer cells, also exhibit Src-dependent, anti-apoptotic proliferation under serum-starved conditions, and that low-density, detergent-insoluble membrane microdomains (MD) serve as a structural platform for signaling events involving p145(met), EGFR, and Src. As an MD-associated molecule that may contribute to bladder carcinoma-specific cellular function, we identified uroplakin IIIa (UPIIIa), an urothelium-specific protein. Results obtained so far revealed: 1) UPIIIa undergoes partial proteolysis in serum-starved cells; 2) a specific antibody to the extracellular domain of UPIIIa inhibits the proteolysis of UPIIIa and the activation of Src, and promotes apoptosis in serum-starved cells; and 3) knockdown of UPIIIa by short interfering RNA also promotes apoptosis in serum-starved cells. GM6001, a potent inhibitor of matrix metalloproteinase (MMP), inhibits the proteolysis of UPIIIa and promotes apoptosis in serum-starved cells. Furthermore, serum starvation promotes expression and secretion of the heparin-binding EGF-like growth factor in a manner that depends on the functions of MMP, Src, and UPIIIa. These results highlight a hitherto unknown signaling network involving a subset of MD-associated molecules in the anti-apoptotic mechanisms of human bladder carcinoma cells.