HtrA2/Omi influences the stability of LON protease 1 and prohibitin,proteins involved in mitochondrial homeostasis

High temperature requirement A2 (HtrA2)/Omi is a serine protease localized in mitochondria. In response to apoptotic stimuli, HtrA2 is released to the cytoplasm and cleaves many proteins, including XIAP, Apollon/BRUCE, WT1, and Ped/Pea-15, to promote apoptosis. However, the function of HtrA2 in mitochondria under normal conditions remains unclear. Here, we show that the mitochondrial proteins, LON protease 1 (LONP1) and prohibitin (PHB), are overexpressed in HtrA2^−/− mouse embryonic fibroblast (MEF) cells and HtrA2 knock-down HEK293T cells. We also confirm the effect of the HtrA2 protease on the stability of the above mitochondrial quality control proteins in motor neuron degeneration 2 (mnd2) mice, which have a greatly reduced protease activity as a result of a Ser276Cys missense mutation of the HtrA2 gene. In addition, PHB interacts with and is directly cleaved by HtrA2. Luminescence assays demonstrate that the intracellular ATP level is decreased in HtrA2^−/− cells compared to HtrA2^+/+ cells. HtrA2 deficiency causes a decrease in the mitochondrial membrane potential, and reactive oxygen species (ROS) generation is greater in HtrA2^−/− cells than in HtrA2^+/+ cells. Our results implicate that HtrA2 might be an upstream regulator of mitochondrial homeostasis.     

Coexposure to environmental tobacco smoke increases levels of allergen-induced airway remodeling in mice

Environmental tobacco smoke (ETS) can increase asthma symptoms and the frequency of asthma attacks. However, the contribution of ETS to airway remodeling in asthma is at present unknown. In this study, we have used a mouse model of allergen-induced airway remodeling to determine whether the combination of chronic exposure to ETS and chronic exposure to OVA allergen induces greater levels of airway remodeling than exposure to either chronic ETS or chronic OVA allergen alone. Mice exposed to chronic ETS alone did not develop significant eosinophilic airway inflammation, airway remodeling, or increased airway hyperreactivity to methacholine. In contrast, mice exposed to chronic OVA allergen had significantly increased levels of peribronchial fibrosis, increased thickening of the smooth muscle layer, increased mucus, and increased airway hyperreactivity which was significantly enhanced by coexposure to the combination of chronic ETS and chronic OVA allergen. Mice coexposed to chronic ETS and chronic OVA allergen had significantly increased levels of eotaxin-1 expression in airway epithelium which was associated with increased numbers of peribronchial eosinophils, as well as increased numbers of peribronchial cells expressing TGF-beta1. These studies suggest that chronic coexposure to ETS significantly increases levels of allergen-induced airway remodeling (in particular smooth muscle thickness) and airway responsiveness by up-regulating expression of chemokines such as eotaxin-1 in airway epithelium with resultant recruitment of cells expressing TGF-beta1 to the airway and enhanced airway remodeling.     

Synthesis of 6-formyl-pyridine-2-carboxylate derivatives and their telomerase inhibitory activities

Twenty-one pyridine-2-carboxylate derivatives were prepared by the coupling of 6-formyl-2-carboxylic acid with the corresponding phenol, thiophenol, and aniline, substituted with various functional groups. Among them, the 3,4-dichlorothiophenol ester (9p) showed the highest in vitro telomerase inhibitory activity and quite significant in vivo tumor suppression activity.     

Two gap junction channel (innexin) genes of the Bombyx mori and their expression

Gap junctions are clusters of intercellular channels that are associated with embryonic development and neural signaling. Innexins, invertebrate gap junction proteins, have been identified in Drosophila and Caenorhabditis. Here, we report the isolation and characterization of two novel members of the insect innexin family, Bm inx2 and Bm inx4, from embryos of the silkworm, Bombyx mori, during the germ-band formation stage. Bm inx2 is a single copy gene with one exon, while Bm inx4 is a single copy gene with four exons and three introns. The predicted proteins show structural similarities with other innexin family members, including four transmembrane (TM) domains, two extracellular loops (ELs), one cytoplasmic loop (CL), and typical conserved amino acids. Bm inx2 is phylogenetically orthologous to the other insect inx2 genes, but Bm inx4 is not orthologous to any known innexin including Dm inx4. Interestingly, Northern blotting and in situ hybridization showed that Bm inx2 was variously expressed across all developmental stages and in various tissues, with high expression seen in the nervous system at the time of embryogenesis. In contrast, Bm inx4 was transiently expressed at the germ-band formation stage of embryogenesis, and was specifically expressed in the ovary and testis during the larval and pupal stages. The isolation and characterization of these novel genes should form the basis for further study of the functional events that occur during development and neuronal communication in B. mori.     

Effect of an Artificial Caudal Fin on the Performance of a Biomimetic Fish Robot Propelled by Piezoelectric Actuators

This paper addresses the design of a biomimetic fish robot actuated by piezoeeramic actuators and the effect of artificial caudal fins on the fish robot＇s performance. The limited bending displacement produced by a lightweight piezocomposite actuator was amplified and transformed into a large tail beat motion by means of a linkage system. Caudal fins that mimic the shape of a mackerel fin were fabricated for the purpose of examining the effect of caudal fm characteristics on thrust production at an operating frequency range. The thickness distribution of a real mackerel＇s fin was measured and used to design artificial caudal fins. The thrust performance of the biomimetic fish robot propelled by fins of various thicknesses was examined in terms of the Strouhal number, the Froude number, the Reynolds number, and the power consumption. For the same fm area and aspect ratio, an artificial caudal fin with a distributed thickness shows the best forward speed and the least power consumption.     

Feedback control of adrenal steroidogenesis via H2O2-dependent, reversible inactivation of peroxiredoxin III in mitochondria

Certain members of the peroxiredoxin (Prx) family undergo inactivation through hyperoxidation of the catalytic cysteine to sulfinic acid during catalysis and are reactivated by sulfiredoxin; however, the physiological significance of this reversible regulatory process is unclear. We now show that PrxIII in mouse adrenal cortex is inactivated by H(2)O(2) produced by cytochrome P450 enzymes during corticosterone production stimulated by adrenocorticotropic hormone. Inactivation of PrxIII triggers a sequence of events including accumulation of H(2)O(2), activation of p38 mitogen-activated protein kinase, suppression of steroidogenic acute regulatory protein synthesis, and inhibition of steroidogenesis. Interestingly, levels of inactivated PrxIII, activated p38, and sulfiredoxin display circadian oscillations. Steroidogenic tissue-specific ablation of sulfiredoxin in mice resulted in the persistent accumulation of inactive PrxIII and suppression of the adrenal circadian rhythm of corticosterone production. The coupling of CYP11B1 activity to PrxIII inactivation provides a feedback regulatory mechanism for steroidogenesis that functions independently of the hypothalamic-pituitary-adrenal axis.