No abstract

Background:The role of Foxf1 in smooth muscle development is unknown. Results: Foxf1 binds to serum response factor and myocardin to regulate transcription and affect contractility of visceral smooth muscle cells. Conclusion: Foxf1 is required for normal development of gastrointestinal smooth muscle. Significance: Forkhead proteins interact with the SRF/myocardin axis to control the phenotype of smooth muscle cells.

SWI/SNF ATP-dependent chromatin-remodeling complexes containing either Brahma-related gene 1 (Brg1) or Brahma (Brm) play important roles in mammalian development. In this study we examined the roles of Brg1 and Brm in smooth muscle development, in vivo, through generation and analysis of mice harboring a smooth muscle-specific knockout of Brg1 on wild-type and Brm null backgrounds. Knockout of Brg1 from smooth muscle in Brg1 flox/flox mice expressing Cre recombinase under the control of the smooth muscle myosin heavy-chain promoter resulted in cardiopulmonary defects, including patent ductus arteriosus, in 30 to 40% of the mice. Surviving knockout mice exhibited decreased expression of smooth muscle-specific contractile proteins in the gastrointestinal tract, impaired contractility, shortened intestines, disorganized smooth muscle cells, and an increase in apoptosis of intestinal smooth muscle cells. Although Brm knockout mice had normal intestinal structure and function, knockout of Brg1 on a Brm null background exacerbated the effects of knockout of Brg1 alone, resulting in an increase in neonatal lethality. These data show that Brg1 and Brm play critical roles in regulating development of smooth muscle and that Brg1 has specific functions within vascular and gastrointestinal smooth muscle that cannot be performed by Brm.The SWI/SNF complex is perhaps the best-characterized mammalian ATP-dependent chromatin-remodeling complex (8). It is comprised of 7 to 11 components, which assemble into distinct complexes containing either Brahma-related gene 1 (Brg1) or Brahma (Brm) ATPase subunits. Brg1 and Brm are ubiquitously expressed in almost all tissues. Studies have suggested that Brg1 and Brm can have either redundant or distinct roles in regulating gene expression. For example, although Brg1 but not Brm has been shown to interact with Crp2 and subsequently induce expression of smooth muscle (SM)-specific genes (4), either Brg1 or Brm has been shown to be sufficient to support the smooth muscle myogenic activity of the myocardin family of activators in SW13 cells (33,34). Data from knockout mice suggest that Brg1-and Brm-containing SWI/SNF complexes are functionally distinct in vivo. Brg1 knockout mice die early in embryonic development during the periimplantation stage (1), while global Brm knockout mice develop normally. On a 129/sv background but not a mixed 129/sv ϫ C57BL/6 background, adult Brm knockout mice exhibited a higher body weight than wild-type (WT) littermates (24).To circumvent the embryonic lethality observed in Brg1 knockout mice, several groups have generated and analyzed tissue-specific Brg1 knockout mice. These studies have revealed unique roles for Brg1-containing SWI/SNF complexes in development of many tissues (5, 11-13, 16, 20, 26). However, few of these studies have determined if Brm also contributes to these developmental pathways. One study combined a tissuespecific Brg1 knockout with a global Brm knockout to show that further loss of Brm did not exacerbate the erythropoietic or endothel...

Our previous study showed that a methanol extract of Inula helenium had the potential to induce detoxifying enzymes such as quinone reductase (QR) and glutathione S-transferase (GST) activity. In this study the methanol extract was further fractionated using silica gel chromatography and vacuum liquid chromatography, to yield pure compounds alantolactone and isoalantolactone as QR inducers. Alantolactone caused a dose-dependent induction of antioxidant enzymes including QR, GST, gamma-glutamylcysteine synthase, glutathione reductase, and heme oxygenase 1 in hepa1c1c7 mouse hepatoma cells. The compound increased the luciferase activity of HepG2-C8 cells, transfectants carrying antioxidant response element (ARE)-luciferase gene, in a dose-dependent manner, suggesting ARE-mediated transcriptional activation of antioxidant enzymes. Alantolactone also stimulated the nuclear accumulation of Nrf2 that was inhibited by phosphatidylinositol 3-kinase (PI3K) inhibitors. In conclusion, alantolactone appears to induce detoxifying enzymes via activation of PI3K and JNK signaling pathways, leading to translocation of Nrf2, and subsequent interaction between Nrf2 and ARE in the encoding genes.

Two diarylheptanoids, oregonin (1) and hirsutanone (2), were isolated by bioassay-guided fractionation of the methanol extracts of the leaves of Alnus japonica Steud and their structures were elucidated from their spectroscopic data. Compounds 1 and 2 exhibited significant low-density lipoprotein (LDL)-antioxidant activities, e. g., thiobarbituric acid-reactive substances (TBARS) assay (1: IC50 = 3.2 microM, 2: IC50 = 1.5 microM), lag time (1 : 162 min, 2 : 230 min at 2.0 microM, control: 63 min), relative electrophoretic mobility (REM, inhibition of 1 : 71%, 2 : 75% at 10 microM), apoB-100 fragmentation (inhibition of 1 : 27.3%, 2 : 40.3% at 10 microM) and macrophage-mediated LDL oxidation (inhibition of 1 : 82%, 2 : 84% at 1 microM).