Pleiotropic Actions of Helicobacter pylori Vacuolating Cytotoxin, VacA
スポンサーリンク
概要
- 論文の詳細を見る
Helicobacter pylori produces a vacuolating cytotoxin, VacA, and most virulent H. pylori strains secrete VacA. VacA binds to two types of receptor-like protein tyrosine phosphatase (RPTP), RPTPα and RPTPβ, on the surface of host cells. VacA bound to RPTPβ, relocates and concentrates in lipid rafts in the plasma membrane. VacA causes vacuolization, membrane anion-selective channel and pore formation, and disruption of endosomal and lysosomal activity in host cells. Secreted VacA is processed into p33 and p55 fragments. The p55 domain not only plays a role in binding to target cells but also in the formation of oligomeric structures and anionic membrane channels. Oral administration of VacA to wild-type mice, but not to RPTPβ knockout mice, resulted in gastric ulcers, in agreement with the clinical effect of VacA. VacA with s1/m1 allele has more potent cytotoxic activity in relation to peptic ulcer disease and appears to be associated with human gastric cancer. VacA activates pro-apoptotic Bcl-2 family proteins, and induces apoptosis via a mitochondria-dependent pathway. VacA can disrupt other signal transduction pathways; VacA activates p38 MAPK, enhancing production of IL-8 and PGE 2, and PI3K/Akt, suppressing GSK-3β activity. VacA has immunomodulatory actions on T cells and other immune cells, possibly contributing to the chronic infection seen with this organism. H. pylori virulence factors including VacA and CagA, which is encoded by cytotoxin-associated gene A, along with host genetic and environmental factors, constitute a complex network to regulate chronic gastric injury and inflammation, which is involved in a multistep process leading to gastric carcinogenesis.
- 2010-01-01
著者
-
Hirayama Toshiya
Department Of Bacteriology Institute Of Tropical Medicine Nagasaki University
-
Isomoto Hajime
長崎大学病院 光学医療診療部
-
Moss Joel
Translational Medicine Branch National Heart Lung And Blood Inst. National Institutes Of Health
-
Hirayama Toshiya
Department Of Bacteriology Institute Of Tropical Medicien Nagasaki University
-
Isomoto Hajime
Department of Pharmacotherapeutics, Nagasaki University Graduate School of Pharmaceutical Science
-
Isomoto Hajime
Department Of Endoscopy Nagasaki University Hospital
-
Moss Joel
Translational Medicine Branch National Heart Lung And Blood Institute National Institutes Of Health
関連論文
- 緑膿菌由来のIL-8誘導蛋白の生物学的活性とその臨床的意義
- Unexpected expression of Hsp47, a replacement of one amino acid (Val 7 Leu) in the amino terminal region, in cultured human tumorigenic cell lines
- Protein tyrosine phosphatase β, a receptor for Helicobacter pylori VacA toxin
- High Molecular Weight Factor in FCS Inhibits Helicobacter pylori VacA-Binding to Its Receptor, RPTPβ, on AZ-521
- Induction of Active Invagination of Plasma Membranes by Helicobacter pylori Cytotoxin, VacA, in Cultured Gastric Cells. An Immunoelectron Microscopic Study.
- Comparison of keratin expression in cultured human adenocarcinoma cell lines
- Method of Gene Delivery into Cells Using Dendritic Poly (L-Lysine)s
- DNA-Binding Abilities of Cationic α-Helix Peptides and Their Transfection Abilities into Cells
- Interaction of Amphiphilic α-Helical Peptides with Phospholipid Membrane and Their DNA Binding Ability
- Spontaneous Regression of Colonic Lesions in Adult T-cell Leukemia
- Helicobacter pylori Vacuolating Cytotoxin, VacA, Is Responsible for Gastric Ulceration
- High-Level Expression of Heat-Stable Enterotoxin (ST) Receptor with Exchange of the Signal Peptide in Baculovirus/Insect Cell System
- Divergence of virulence factors of Helicobacter pylori among clinical isolates dose not correlate with disease specificity
- Development of Hyperfimbriated Strains of Vibrio cholerae O1
- Pleiotropic Actions of Helicobacter pylori Vacuolating Cytotoxin, VacA
- Predictive Value of the Fibrosis Scores in Patients with Chronic Hepatitis C Associated with Liver Fibrosis and Metabolic Syndrome
- Effect of an oral branched chain amino acid-enriched snack in cirrhotic patients with sleep disturbance
- MAGNIFYING ENDOSCOPIC OBSERVATION WITH NARROW BAND IMAGING FOR SPECIALIZED INTESTINAL METAPLASIA IN BARRETT'S ESOPHAGUS WITH SPECIAL REFERENCE TO LIGHT BLUE CRESTS
- Advantages of laserphyrin compared with photofrin in photodynamic therapy for bile duct carcinoma.
- Geranylgeranylacetone has anti-hepatitis C virus activity via activation of mTOR in human hepatoma cells
- Successful Management of Cap Polyposis with Eradication of Helicobacter pylori Relapsing 15 Years after Remission on Steroid Therapy