Molecular mechanisms regulating extracellular matrix-mediated remodeling in the ductus arteriosus.

Progressive remodeling throughout the fetal and postnatal period is essential for anatomical closure of the ductus arteriosus (DA). Internal elastic lamina interruption and subendothelial region widening, elastic fiber formation impairment in the tunica media, and intimal thickening are distinctive features of the fetal DA. After birth, the DA undergoes further extracellular matrix-mediated remodeling. Based on the knowledge obtained from mouse models and human disease, recent studies revealed a molecular mechanism of DA remodeling. In this review, we focus on matrix remodeling and regulation of cell migration/proliferation associated with DA anatomical closure and discuss the role of prostaglandin E receptor 4 (EP4) signaling and jagged1-Notch signaling as well as myocardin, vimentin, and secretory components including tissue plasminogen activator, versican, lysyl oxidase, and bone morphogenetic proteins 9 and 10.

Effects of Interfacial Interactions on Electrocatalytic Activity of Cytochrome c Oxidase in Biomimetic Lipid Membranes on Gold Electrodes.

Effects of interfacial interactions on the electrocatalytic activity of protein-tethered bilayer lipid membranes (ptBLMs) containing cytochrome c oxidase (CcO) for the oxygen reduction reaction are studied by using protein film electrochemistry and surface-enhanced infrared absorption (SEIRA) spectroscopy. Mammalian CcO was immobilized on a gold electrode via self-assembled monolayers (SAMs) of mixed alkanethiols. The protein orientation on the electrode is controlled by SAM-CcO interactions and is critical to the cytochrome c (cyt c) binding. The CcO-phospholipid and CcO-cyt c interactions modulate the electrocatalytic activity of CcO, and more densely packed ptBLMs show higher electrocatalytic activity. Our study indicates that spectroscopic and electrochemical studies of ptBLMs can provide insights into the effects of relatively weak protein-protein and protein-lipid interactions on the enzymatic activity of transmembrane enzymes.

Transcriptome Analysis Reveals Differential Gene Expression between the Closing Ductus Arteriosus and the Patent Ductus Arteriosus in Humans.

The ductus arteriosus (DA) immediately starts closing after birth. This dynamic process involves DA-specific properties, including highly differentiated smooth muscle, sparse elastic fibers, and intimal thickening (IT). Although several studies have demonstrated DA-specific gene expressions using animal tissues and human fetuses, the transcriptional profiles of the closing DA and the patent DA remain largely unknown. We performed transcriptome analysis using four human DA samples. The three closing DA samples exhibited typical DA morphology, but the patent DA exhibited aorta-like elastic lamellae and poorly formed IT. A cluster analysis revealed that samples were clearly divided into two major clusters, the closing DA and patent DA clusters, and showed distinct gene expression profiles in IT and the tunica media of the closing DA samples. Cardiac neural crest-related genes such as JAG1 were highly expressed in the tunica media and IT of the closing DA samples compared to the patent DA sample. Abundant protein expressions of jagged 1 and the differentiated smooth muscle marker calponin were observed in the closing DA samples but not in the patent DA sample. Second heart field-related genes such as ISL1 were enriched in the patent DA sample. These data indicate that the patent DA may have different cell lineages compared to the closing DA.

Isolation, synthesis, and biological activities of a bibenzyl from Empetrum nigrum var. japonicum.

4-(2-Hydroxyphenethyl)-2,6-dimethoxyphenol, a bibenzyl, was isolated from the leaves of Empetrum nigrum var. japonicum, collected from Mount Tateyama. Japanese rock ptarmigans frequently eat the leaves and fruits of this plant. The structure of the bibenzyl was confirmed by NMR spectroscopic analysis and fully characterized. A synthesis of this compound was accomplished by coupling 2-hydroxyphenylacetic acid with syringaldehyde, decarboxylation of the resultant isoaurones, and hydrogenation of the double bond in the corresponding stilbene. This compound displayed cytotoxic activity against human cancer cells (HCT116 and Hela cells) and leukemia cells (HL-60 cells). The present study suggests that this plant serves as a source of biologically active natural products. Also, our findings provide information on the secondary metabolites in the diet of Japanese rock ptarmigans.