Yamazaki J.,Fukuoka Dental College
Yakugaku Zasshi | Year: 2016
Cl- -permeable channels and transporters expressed on the cell membranes of various mammalian cell types play pivotal roles in the transport of electrolytes and water, pH regulation, cell volume and membrane excitability, and are therefore expected to be useful molecular targets for drug discovery. Both TMEM16A (a possible candidate for Ca2+- regulated Cl- channels recently identified) and cystic fibrosis transmembrane conductance regulator (CFTR) (or cAMP-regulated Cl- channels) have been known to be involved in Cl- secretion and reabsorption in the rat salivary gland. Crosstalk between two types of regulatory pathways through these two types of channels has also been described. Previously, we demonstrated that CLCA, a Ca2+-activated Cl- channel modulator, was involved in Cl- absorption in rat salivary ducts. In addition to Ca2+, basal NF-κB activity in a mouse keratinocyte line was shown to be involved in the transcriptional regulation of CLCA. Conversely, a truncated isoform of CLCA was found in undifferentiated epithelial cells present in the rat epidermal basal layers. Under regulation by Ca2+ and PKC, the surface expression of β1-integrin and cell adhesion were decreased in the CLCA-overexpressing cells. Knockdown of this isoform elevated the expression of β1-integrin in rat epidermis in vivo. These results indicate that the specific differentiation-dependent localization of CLCA, and transcriptional regulation through Ca2+, are likely to affect ion permeability and the adhesive potential of epithelial cells. In summary, these types of Cl- channels and their modulators may function in a coordinated manner in regulating the functions of epithelial cells under different physiological conditions. © 2016 The Pharmaceutical Society of Japan.
Ooboshi H.,Fukuoka Dental College
Nature Medicine | Year: 2017
Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb. Combined deficiency for Msr1 and Marco, or for Mafb alone, in infiltrating myeloid cells caused impaired clearance of DAMPs, more severe inflammation, and exacerbated neuronal injury in a murine model of ischemic stroke. The retinoic acid receptor (RAR) agonist Am80 increased the expression of Mafb, thereby enhancing MSR1 expression. Am80 exhibited therapeutic efficacy when administered, even at 24 h after the onset of experimental stroke. Our findings uncover cellular mechanisms contributing to DAMP clearance in resolution of the sterile inflammation triggered by tissue injury. © 2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Ooboshi H.,Fukuoka Dental College
Current Pharmaceutical Design | Year: 2011
Cerebrovascular disease is the leading cause of death and disability in Japan and most Western countries. Gene transfer techniques may be applicable to the treatment of serious types of stroke, since several experimental studies have revealed the usefulness of gene therapy in the protection of neurons, reduction of infarct size and improvement of function. Prevention of vasospasm after subarachnoid hemorrhage is one of the best candidates for vascular gene therapy. Ischemia-induced apoptosis, inflammation, and derangement of neurovascular units can be targeted by the gene transfer approach. Recent studies have shown that promotion of neurogenesis and functional recovery may also be achieved by this strategy. Furthermore, a combination of stem cell therapy with gene transfer methods may be feasible. This review describes novel approaches for the treatment of stroke using gene transfer techniques. © 2011 Bentham Science Publishers Ltd.
Sawa Y.,Fukuoka Dental College
Japanese Dental Science Review | Year: 2010
Podoplanin is a mucin-type glycoprotein firstly identified in podocytes, which is homologous to the type I alveolar cell specific T1α-2 antigen and to the oncofetal antigen M2A recognized by the D2-40 antibody. Podoplanin possesses a platelet aggregation-stimulating domain causes the platelet aggregation on cancer cells by the binding activity to CLEC-2. Podoplanin also contributes to the formation of membrane-actin structures. The increased podoplanin expression is found in squamous cell carcinomas at the invasive edge. It has been reported that the podoplanin induces an actin cytoskeleton rearrangement dependent on the RhoA GTPase activation to phosphorylate ezrin and facilitates an epithelial-mesenchymal transition (EMT) which induces the single cell migration of cancer cells. However, the podoplanin-expressing cancer cells often express E-cadherin and migrate in a collective manner, suggesting that there are podoplanin-induced alternative pathways for the actin cytoskeleton rearrangement independent of the RhoA activation and EMT. The strong expression of podoplanin is present in salivary gland myoepithelial cells, and in enamel epithelia and odontoblasts of the tooth germ for a bell stage. Podoplanin may act as a cell morphological regulator in normal and cancer cells. © 2010 Japanese Association for Dental Science.
Islam M.R.,Kyushu University |
Nagao J.-I.,Fukuoka Dental College |
Zendo T.,Kyushu University |
Sonomoto K.,Kyushu University
Biochemical Society Transactions | Year: 2012
Lantibiotics are ribosomally synthesized antimicrobial peptides that commonly target the cell wall precursor lipid II during their antimicrobial mechanism and exert their inhibitory activity by (i) inhibition of cell wall biosynthesis, and (ii) stable pore formation in the target membrane. Type-A(I) (i.e. nisin) and two-component (i.e. lacticin 3147) lantibiotics initially interact with lipid II to stabilize the complex, which then proceeds to inhibit cell wall biosynthesis and pore formation. Type-A(II) (i.e. nukacin ISK-1) and type-B (i.e. mersacidin) lantibiotics also use lipid II as a docking molecule, but can only inhibit cell wall biosynthesis without forming pores. In the present paper, we review the antimicrobial mechanism of different types of lantibiotics, their current progress and future prospect. ©The Authors Journal compilation ©2012 Biochemical Society.
Kawaguchi M.,Fukuoka Dental College
International journal of nanomedicine | Year: 2011
Carbon nanotubes act as a photon antenna that serves as an effective "molecular heater" around the near-infrared (NIR) region. This exothermic generation can be used as a possible heating source for hyperthermia therapy. The current study reports the dispersible and exothermic properties with NIR irradiation for single-walled carbon nanotubes (SWNTs) treated with a strong acid (acid-treated SWNTs), and the SWNTs further functionalized with double-stranded DNA (DNA-functionalized SWNTs: DNA-SWNTs). DNA-SWNTs significantly improved the dispersibility of SWNTs when compared with the acid-treated SWNTs. The binding ratio of the acid-treated SWNT and DNA was calculated to be 3.1 (DNA/SWNTs) from the phosphorous content in the DNA-SWNT. This interaction of the SWNTs and DNA would contribute to the stable dispersion of the DNA-SWNTs in a culture medium. With NIR irradiation by a halogen lamp light source, the acid-treated SWNTs and the DNA-SWNTs showed strong heat evolution in vitro (in a culture medium) and in vivo (in the subcutaneous tissue of a mouse) condition without any invasive effect on the non-SWNT area. The results of this study suggested that the functionalization with DNA was an efficient approach to improve the dispersibility of SWNTs in body fluids, and the DNA-SWNT would be a promising source for photo-induced exothermic generation.
Ohkubo T.,Fukuoka Dental College |
Yamazaki J.,Fukuoka Dental College
International Journal of Oncology | Year: 2012
T-type voltage-gated Ca 2+ channels have unique electrophysiological properties, suitable for generating Ca 2+ oscillations and waves and thus controlling the proliferation of various tumor cells. In the present study, we investigated the role of Ca v3.1, a candidate tumor suppressor gene, in neoplastic processes, and compared the differences between Ca v3.1 with Ca v3.2 channels. While the overexpression of a full-length Ca v3.1 clone suppressed cell proliferation, the knockdown of the Ca v3.1 gene by siRNA, or treatment with ProTx-I, a relatively selective inhibitor for Cav3.1, promoted the cell proliferation of MCF-7 cells (a human breast adenocarcinoma cell line). Although Ca v3.1 and Ca v3.2 channels possess comparable biophysical properties and are often co-expressed in various tissues, gene knockdown or the overexpression of Ca v3.2 channels exhibited no effect on cell proliferation. Using immunocytochemical co-staining, the Cav3.1 channels were specifically visualized in the plasma membranes of apoptotic cells, identified by Annexin V and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assays and nuclear condensation. On the contrary, Ca v3.2 channels were expressed at the membrane of large portions of cells, with no likely relation to Ca v3.1 expression or apoptosis. An apoptosis assay revealed that the overexpression of the Ca v3.1 clone caused an increase in the number of apoptotic cells. Furthermore, Ca v3.1 knockdown blocked cyclophosphamide-induced apoptosis. These results suggest that Ca v3.1 channels may contribute to the repression of tumor proliferation and the promotion of apoptosis mediated via Ca v3.1-specific Ca 2+ influx.
Kajiya H.,Fukuoka Dental College
Advances in Experimental Medicine and Biology | Year: 2012
Calcium (Ca 2+) signaling controls multiple cellular functions and is regulated by the release of Ca 2+ from internal stores and its entry from the extracellular fluid. Ca 2+ signals in osteoclasts are essential for diverse cellular functions including differentiation, bone resorption and gene transcription. Recent studies have highlighted the importance of intracellular Ca 2+ signaling for osteoclast differentiation. Receptor activator of NF-κB ligand (RANKL) signaling induces oscillatory changes in intracellular Ca 2+ concentrations, resulting in Ca 2+/calcineurin-dependent dephosphorylation and activation of nuclear factor of activated T cells c1 (NFATc1), which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. Recently, some reports indicated that RANKL-induced Ca 2+ oscillation involved not only repetitive intracellular Ca 2+ release from inositol 1, 4, 5-triphosphate channels in Ca 2+ store sites, but also via store-operated Ca 2+ entry and Ca 2+ entry via transient receptor potential V channels during osteoclast differentiation. Ca 2+-regulatory cytokines and elevation of extracellular Ca 2+ concentrations have been shown to increase intracellular Ca 2+ concentrations ([Ca 2+] i) in mature osteoclasts, regulating diverse cellular functions. RANKL-induced [Ca 2+] i increase has been reported to inhibit cell motility and the resorption of cytoskeletal structures in mature osteoclasts, resulting in suppression of bone-resorption activity. In conclusion, Ca 2+ signaling activates differentiation in osteoclast precursors but suppresses resorption in mature osteoclasts. This chapter focuses on the roles of long-term Ca 2+ oscillations in differentiation and of short-term Ca 2+ increase in osteoclastic bone resorption activity. © 2012 Springer Science+Business Media B.V.
Shimada K.,Fukuoka Dental College
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012
An associative classification method for incomplete database is proposed based on an evolutionary rule extraction method. The method can extract class association rules directly from the database including missing values and build an associative classifier. Instances including missing values are classified by the classifier. In addition, an evolving associative classifier is proposed. The proposed method evolves the classifier using the labeled instances by itself as acquired information. The performance of the classification was evaluated using artificial incomplete data set. The results showed that the proposed evolving associative classifier has a potential to expand the target data for classification through its evolutionary process and gather useful information itself. © 2012 Springer-Verlag.
Ikebe T.,Fukuoka Dental College
Oral Science International | Year: 2013
Since the first article about bisphosphonate-related osteonecrosis of the jaw (BRONJ) was published in 2003, clinical and basic research for BRONJ has continued worldwide to understand this novel disease. Several organizations have proposed the definition, diagnostic criteria, risk factors, and treatment strategy for BRONJ. Recently, some new drugs used for cancer patients such as bevacizumab and sunitinib have also been reported to be involved in osteonecrosis of the jaw (ONJ). Because ONJ appears to be initially derived from osteoclast inhibition, a new category of diseases named as " drug-related osteoclastic disease of the jaw" may be assumed. Considering the accumulated knowledge related to BRONJ, including osteoclast biology, bisphosphonate pharmacology, animal experiments, and clinicopathological findings, a perspective of BRONJ from the pathophysiological viewpoint is proposed in this review. © 2012 Japanese Stomatological Society.