Dual Roles of Gastric Gland Mucin-specific O-glycans in Prevention of Gastric Cancer

Gastric gland mucin is secreted from gland mucous cells, including pyloric gland cells and mucous neck cells located in the lower layer of the gastric mucosa. These mucins typically contain O-glycans carrying terminal alpha 1,4-linked N-acetylglucosamine residues (alpha GlcNAc) attached to the scaffold protein MUC6, and biosynthesis of the O-glycans is catalyzed by the glycosyltransferase, alpha 1,4-N-acetylglucosaminyltransferase (alpha 4GnT). We previously used expression cloning to isolate cDNA encoding alpha 4GnT, and then demonstrated that aGlcNAc functions as natural antibiotic against Helicobacter pylori, a microbe causing various gastric diseases including gastric cancer. More recently, it was shown that aGlcNAc serves as a tumor suppressor for differentiated-type adenocarcinoma. This review summarizes these findings and identifies dual roles for aGlcNAc in gastric cancer.ArticleACTA HISTOCHEMICA ET CYTOCHEMICA. 47(1):1-9 (2014)journal articl

Physiological Roles of Class I HDAC Complex and Histone Demethylase

Epigenetic gene silencing is one of the fundamental mechanisms for ensuring proper gene expression patterns during cellular differentiation and development. Histone deacetylases (HDACs) are evolutionally conserved enzymes that remove acetyl modifications from histones and play a central role in epigenetic gene silencing. In cells, HDAC forms a multiprotein complex (HDAC complex) in which the associated proteins are believed to help HDAC carry out its cellular functions. Though each HDAC complex contains distinct components, the presence of isoforms for some of the components expands the variety of complexes and the diversity of their cellular roles. Recent studies have also revealed a functional link between HDAC complexes and specific histone demethylases. In this paper, we summarize the distinct and cooperative roles of four class I HDAC complexes, Sin3, NuRD, CoREST, and NCoR/SMRT, with respect to their component diversity and their relationship with specific histone demethylases

Nox4-generated ROS Regulate TGF-β1-induced Motility of Colon Cancer Cells through the Low Molecular Weight Protein Tyrosine Phosphatase-Rho Signaling Pathway

Article信州医学雑誌 63(5):281-293 (2015)journal articl

Role of Sulfated O-Glycans Expressed by High Endothelial Venule-Like Vessels in Pathogenesis of Chronic Inflammatory Gastrointestinal Diseases

Lymphocyte homing is mediated by a cascade of adhesive interactions between circulating lymphocytes and specialized endothelial cells comprising high endothelial venules (HEVs). Sulfated O-glycans expressed on HEVs, collectively called peripheral lymph node addressin (PNAd), interact with L-selectin expressed on lymphocytes, contributing to the initial step of the lymphocyte homing. In chronic inflammatory states, PNAd is induced on HEV-like vessels but absent in non-lymphoid tissues under normal conditions. Such HEV-like vessels have been observed in various chronic inflammatory diseases including rheumatoid arthritis, lymphocytic thyroiditis, Helicobacter pylori-associated chronic gastritis, and inflammatory bowel disease (IBD), and implicated in lymphocyte recruitment in those diseases. In H. pylori-associated chronic gastritis, PNAd-expressing HEV-like vessels are induced, and the progression of chronic inflammation is highly correlated with appearance of these vessels. Furthermore, eradication of H. pylori by antibiotics resulted in disappearance of PNAd. These results indicate that inhibition of PNAd formation could have therapeutic effect by attenuating lymphocyte recruitment. In ulcerative colitis (UC), PNAd-expressing HEV-like vessels are induced, preferentially in the active phase, and T cells, particularly CD4(+) T cells, are closely associated with these vessels, suggesting that T cell recruitment via PNAd-expressing HEV-like vessels plays at least a partial role in UC pathogenesis. Additionally, N-acetylglucosamine-6-O-sulfotransferase I (GlcNAc6ST-1) is suggested to be a candidate to regulate PNAd induction on HEV-like vessels in UC. These results provide a potential therapeutic strategy to treat UC by blocking T cell adhesion to PNAd-expressing HEV-like vessels. Inhibition or down-regulation of GlcNAc6ST-1 may be an alternative.ArticleBIOLOGICAL & PHARMACEUTICAL BULLETIN. 32(5):774-779 (2009)journal articl