Recent studies have shown that chronic beta-adrenergic receptor (beta-AR) stimulation alters cardiac myocyte survival in a receptor subtype-specific manner. We examined the effect of selective beta(1)- and beta(2)-AR subtype stimulation on apoptosis induced by hypoxia or H(2)O(2) in rat neonatal cardiac myocytes. Although neither beta(1)- nor beta(2)-AR stimulation had any significant effect on the basal level of apoptosis, selective beta(2)-AR stimulation protected myocytes from apoptosis. beta(2)-AR stimulation markedly increased mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activation as well as phosphatidylinositol-3'-kinase (PI-3K) activity and Akt/protein kinase B phosphorylation. beta(1)-AR stimulation also markedly increased MAPK/ERK activation but only minimally activated PI-3K and Akt. Pretreatment with pertussis toxin blocked beta(2)-AR-mediated protection from apoptosis as well as the beta(2)-AR-stimulated changes in MAPK/ERK, PI-3K, and Akt/protein kinase B. The selective PI-3K inhibitor, LY 294002, also blocked beta(2)-AR-mediated protection, whereas inhibition of MAPK/ERK activation at an inhibitor concentration that blocked agonist-induced activation but not the basal level of activation had no effect on beta(2)-AR-mediated protection. These findings demonstrate that beta(2)-ARs activate a PI-3K-dependent, pertussis toxin-sensitive signaling pathway in cardiac myocytes that is required for protection from apoptosis-inducing stimuli often associated with ischemic stress.

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Many natural polymeric materials are perfect monodisperse macromolecules and are produced by the successive condensation of monomers with polymer end groups that are activated by enzymes. [1][2][3][4] Although these syntheses proceed via many complicated and tightly controlled processes, the overall process could be regarded as a kind of chain-growth polycondensation. In the polycondensation of artificial monomers, however, macromolecules with a wide range of molecular weights have been synthesized, because there is little difference of reactivity between monomers and polymer end groups, and step-growth polymerization occurs. If the polymer end groups become more reactive than monomers and the reaction of monomers with each other is prevented, chain-growth polycondensation would take place to yield artificial condensation polymers having well-defined molecular weights and narrow molecular weight distributions (MWD). Kinetic studies showed that some polycondensations involve more reactive polymer end groups than monomers, but the MWD of polymers were not evaluated. 5 The synthesis of poly-(2,6-dimethyl-1,4-phenylene oxide) by oxidative polymerization of 2,6-dimethylphenol 6 and by phase transfer catalyzed polycondensation of 4-bromo-2,6-dimethylphenynol 7 also involved the reactive polymer end groups and did not show the behavior of a classic polycondensation. Percec conducted this polycondensation in the presence of chain initiators and obtained well-defined polyphenylene oxides. 7 However, the molecular weight values were much higher than the calculated values based on the [monomer]/[initiator] ratios, and polymers having a narrow MWD were obtained after precipitation; the crude polymerization mixture had a broad MWD. In the polycondensations of bifunctional nucleophilic monomers with bifunctional electrophilic monomers, polymers having a low polydispersity (M w /M n < 1.3) were also prepared by phase transfer catalyst (PTC) techniques when polymer end groups were more reactive than monomers. 8-10 This type of polycondensation, however, could not control the molecular weight.Our previous work has shown that the Pd-catalyzed polycondensation of 4-bromo-2-octylphenol and carbon monoxide underwent chain-growth polycondensation from an initiator in the initial stage. 11 Another approach to chain-growth polycondensation was the polycondensation of solid monomer with PTC in organic solvent containing an initiator, where the reaction of monomers with each other was prevented. 12 The molecular weight was controlled but the MWD was a little broad (M w /M n < 1.3). We now report the successful chain-growth polycondensation of phenyl 4-aminobenzoate derivatives 1 for aromatic polyamides having precisely controlled molecular weights and quite narrow MWD (M w /M n < 1.12), where all of the experimental criteria of a living polymerization are exhibited even in polycondensation.The expected course of polymerization of silylated 1a with CsF in the presence of a small amount of reactive initiator 2 bearing an electron-withdrawin...

Abstract-The interaction between macrophages and oxidatively modified low density lipoprotein (Ox-LDL) appears to play a central role in the development of atherosclerosis, not only through foam cell formation but also via the induction of numerous cytokines and growth factors. The current study demonstrated that Ox-LDL upregulated vascular endothelial growth factor (VEGF) mRNA expression in RAW 264 cells, a monocytic cell line, in a time-and concentration-dependent manner and that Ox-LDL stimulated VEGF protein secretion from the cells. Lysophosphatidylcholine, a component of Ox-LDL, also enhanced VEGF mRNA expression in RAW 264 cells and VEGF secretion from RAW 264 cells, with a maximal effect at a concentration of 10 mol/L lysophosphatidylcholine. Immunohistochemical studies showed that human early atherosclerotic lesions exhibited intense VEGF immunoreactivity in subendothelial macrophage-rich regions of the thickened intima. In atherosclerotic plaques, VEGF staining was also observed in foam cell-rich regions adjacent to the lipid core or the neovascularized basal regions of plaque consisting predominantly of smooth muscle cells. High-power-field observation revealed that VEGF was localized in the extracellular space as well as at the macrophage cell surface. These observations suggest the possible involvement of Ox-LDL in the development of human atherosclerosis through VEGF induction in macrophages. (Arterioscler Thromb