Objective-Vascular smooth muscle cells (VSMCs) can switch between differentiated and dedifferentiated phenotypes, and this phenotype switch is believed to be essential for repair of vascular injury. We studied the inhibitory effect of smooth muscle 22␣ (SM22␣) on VSMC proliferation in vitro and in vivo and explored the potential molecular mechanisms of this effect. Methods and Results-By using coimmunoprecipitation and glutathione S-transferase pull-down assays, we have shown that SM22␣ binds to Ras in SM22␣-overexpressed VSMCs in the presence or absence of platelet-derived growth factor-BB stimulation. SM22␣ arrested cell cycle progression through segregation of Ras with Raf-1 and downregulation of the Raf-1-MEK1/2-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling cascade. The inhibitory effect of SM22␣ on VSMC proliferation was verified in vivo. The infection of rat carotid arteries with recombinant adenovirus encoding SM22␣ inhibited neointimal hyperplasia via suppression of the Raf-1-MEK1/ 2-extracellular signal-regulated kinase 1/2 signaling pathway. Conclusion-These findings suggest that high expression of SM22␣ inhibits cell proliferation via reduction of the response to mitogen stimuli in VSMCs and provide a novel mechanism by which VSMCs maintain their contractile phenotype and resist mitogenic stimuli in an SM22␣-dependent manner.

This study focuses on the homogeneous gas-phase formation of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) from the 2,4,6-trichlorophenol (2,4,6-TCP) and 2,4-dichlorophenol (2,4-DCP) precursors, which were found both in the gas phase and in the fly ash samples as the dominating chlorophenol congeners in municipal waste incinerators (MWIs). Molecular orbital theory calculations have been performed for the formation mechanism. The geometrical parameters and vibrational frequencies of all the stationary points were calculated at the MPWB1K level with the 6-31+G(d,p) basis set. Single-point energy calculations were carried out at the MPWB1K/6-311+G(3df,2p) level of theory. Canonical variational transition-state (CVT) theory with small curvature tunneling (SCT) contribution was used to predict the rate constants of crucial elementary steps over the temperature range of interest (600-1200 K). The rate-temperature formulas were fitted for the first time. The pre-exponential factor, the activation energy, and the rate constants are reported. This study shows that at least one chlorine substituent in the ortho position is needed for the formation of PCDDs from the condensation of chlorophenols. The results presented here should help to clarify and detail the formation mechanism of PCDD/PCDFs (PCDD/Fs for short) from chlorophenol precursors in real waste combustion.

No abstract

No abstract