O-GlcNAc Modification of NFκB p65 Inhibits TNF-α-Induced Inflammatory Mediator Expression in Rat Aortic Smooth Muscle Cells

BACKGROUND: We have shown that glucosamine (GlcN) or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) treatment augments O-linked-N-acetylglucosamine (O-GlcNAc) protein modification and attenuates inflammatory mediator expression, leukocyte infiltration and neointima formation in balloon injured rat carotid arteries and have identified the arterial smooth muscle cell (SMC) as the target cell in the injury response. NFκB signaling has been shown to mediate the expression of inflammatory genes and neointima formation in injured arteries. Phosphorylation of the p65 subunit of NFκB is required for the transcriptional activation of NFκB. This study tested the hypothesis that GlcN or PUGNAc treatment protects vascular SMCs against tumor necrosis factor (TNF)-α induced inflammatory stress by enhancing O-GlcNAcylation and inhibiting TNF-α induced phosphorylation of NFκB p65, thus inhibiting NFκB signaling. METHODOLOGY/PRINCIPAL FINDINGS: Quiescent rat aortic SMCs were pretreated with GlcN (5 mM), PUGNAc (10(-4) M) or vehicle and then stimulated with TNF-α (10 ng/ml). Both treatments inhibited TNF-α-induced expression of chemokines [cytokine-induced neutrophil chemoattractant (CINC)-2β and monocyte chemotactic protein (MCP)-1] and adhesion molecules [vascular cell adhesion molecule (VCAM)-1 and P-Selectin]. Both treatments inhibited TNF-α induced NFκB p65 activation and promoter activity, increased NFκB p65 O-GlcNAcylation and inhibited NFκB p65 phosphorylation at Serine 536, thus promoting IκBα binding to NFκB p65. CONCLUSIONS: There is a reciprocal relationship between O-GlcNAcylation and phosphorylation of NFκB p65, such that increased NFκB p65 O-GlcNAc modification inhibits TNF-α-Induced expression of inflammatory mediators through inhibition of NFκB p65 signaling. These findings provide a mechanistic basis for our previous observations that GlcN and PUGNAc treatments inhibit inflammation and remodeling induced by acute endoluminal arterial injury

Applications of planar-chiral phosphaferrocene-oxazolines in asymmetric catalysis and enantioselective desymmetrization by carbon nucleophiles in the presence of chiral ligands

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2003.Includes bibliographical references.In PART I, the design and the synthesis of planar-chiral phosphaferrocene-oxazolines, a new class of P,N-ligands, are described. The modular nature of their structure allows easy access to a number of analogues in enantiomerically pure forms, facilitating the easy tunability of the chiral environment. These ligands are then applied to several transition metal-catalyzed asymmetric reactions. In Pd-catalyzed asymmetric allylic alkylations, it is established that the planar chirality of the phosphaferrocene, not the central chirality of the oxazoline subunit, is the dominant stereocontrol element. On the other hand, in Cu-catalyzed asymmetric reactions (conjugate additions of diethylzinc to acyclic enones, intramolecular Kinugasa reactions for polycyclic β-lactam synthesis, and [3+2] dipolar cycloadditions of azomethine imines to terminal alkynes), it is demonstrated that the central chirality of the oxazoline subunit is the dominant stereocontrol element, and that the planar chirality of the phosphaferrocene plays a subordinate, although significant, role. In PART II, the enantioselective desymmetrization of cyclic anhydrides and imides by carbon nucleophiles is described. By employing a Grignard reagent/chiral ligand complex as the nucleophile, a range of anhydrides and imides are effectively desymmetrized with uniformly high enantiomeric excess. In these reactions, (-)- sparteine is shown to be the ligand of choice for anhydride substrates, whereas a bisoxazoline is found to be most effective for imide substrates.by Ryo Shintani.Ph.D

Synthesis of Poly(arylenevinylene)s by Rhodium-Catalyzed Stitching Polymerization/Alkene Isomerization

Poly­(arylenevinylene)­s constitute an important class of π-conjugated polymers for their potential utility as optoelectronic materials. Herein, we developed a sequence of rhodium-catalyzed stitching polymerization of 1,2-dialkynyl­(hetero)­arenes and aromatization-driven alkene isomerization for the synthesis of new poly­(arylenevinylene)­s. The polymerization and subsequent alkene isomerization proceeded smoothly with high degree of stitching efficiency by employing a Rh/tfb complex as the catalyst, and not only diynes but also triynes and tetraynes could be polymerized to give poly­(arylenevinylene)­s that are not easily accessible by existing synthetic methods. The polymers obtained by the present method were thermally stable, and their optical properties could be varied depending on the repeating unit structure

Copper-Catalyzed Hydroboration of Carbon Dioxide

A copper/N-heterocyclic carbene catalyzed hydroboration of carbon dioxide has been developed to give a formic acid derivative selectively under mild conditions. Investigations directed toward understanding the catalytic cycle of this process have been carried out, and the hydroboration product can be directly used as a formylation reagent for various amines

Rhodium-Catalyzed Polymerization of 3,3-Diarylcyclopropenes Involving a 1,4-Rhodium Migration

A new mode of metal-catalyzed polymerization reaction has been developed by exploiting the ability of 1,4-rhodium migration of an organorhodium­(I) species. Specifically, it has been demonstrated that 3,3-diarylcyclopropenes undergo polymerization through an insertion–1,4-rhodium migration sequence by using an arylrhodium­(I) initiator/catalyst to give poly­(cyclopropylene-<i>o</i>-phenylene)­s, which are difficult to synthesize by conventional polymerization methods

Rhodium-Catalyzed Stitching Reaction: Convergent Synthesis of Quinoidal Fused Oligosiloles

Quinoidal fused oligosiloles, a new family of silicon-bridged π-conjugated compounds, have been synthesized for the first time based on a new synthetic strategy, a stitching reaction. Multiple carbon–carbon bonds can be formed consecutively between two oligo­(silylene-ethynylene)­s under rhodium catalysis in a stitching manner, and up to five siloles have been fused in a quinoidal form. Physical properties of these oligosiloles have also been investigated to find a unique trend in their LUMO levels, which become higher with longer π-conjugation

Rhodium-Catalyzed Stitching Reaction: Convergent Synthesis of Quinoidal Fused Oligosiloles

Quinoidal fused oligosiloles, a new family of silicon-bridged π-conjugated compounds, have been synthesized for the first time based on a new synthetic strategy, a stitching reaction. Multiple carbon–carbon bonds can be formed consecutively between two oligo­(silylene-ethynylene)­s under rhodium catalysis in a stitching manner, and up to five siloles have been fused in a quinoidal form. Physical properties of these oligosiloles have also been investigated to find a unique trend in their LUMO levels, which become higher with longer π-conjugation

Asymptotic Inference for Dynamic Panel Estimators of In nite Order Autoregressive Processes

In this paper we consider the estimation of a dynamic panel autoregressive (AR) process of possibly in nite order in the presence of individual effects. We utilize the sieve AR approximation with its lag order increasing with the sample size. We establish the consistency and asymptotic normality of the standard dynamic panel data estimators, including the xed effects estimator, the generalized methods of moments estimator and Hayakawa's instrumental variables estimator, using double asymptotics under which both the cross-sectional sample size and the length of time series tend to infinity. We also propose a biascorrected fixed effects estimator based on the asymptotic result. Monte Carlo simulations demonstrate that the estimators perform well and the asymptotic approximation is useful. As an illustration, proposed methods are applied to dynamic panel estimation of the law of one price deviations among US cities

The quality of information support analysis of business enterprises

В публікації розглядається основні характеристики інформаційного забезпечення діяльності підприємства.This publication is considered the main characteristics of the enterprise information supply