title: Spermine oxidase, a polyamine catabolic enzyme that links Helicobacter pylori CagA and gastric cancer risk.
abstract: We have recently reported that Helicobacter pylori strains expressing the virulence factor cytotoxin-associated gene A (CagA) stimulate increased levels of spermine oxidase (SMO) in gastric epithelial cells, while cagA⁻ strains did not. SMO catabolizes the polyamine spermine and produces H₂O₂ that results in both apoptosis and DNA damage. Exogenous overexpression of CagA confirmed these findings, and knockdown or inhibition of SMO blocked CagA-mediated apoptosis and DNA damage. The strong association of SMO, apoptosis, and DNA damage was also demonstrated in humans infected with cagA⁺, but not cagA⁻ strains. In infected gerbils and mice, DNA damage was CagA-dependent and only present in epithelial cells that expressed SMO. We also discovered SMO (high) gastric epithelial cells from infected animals with dysplasia that are resistant to apoptosis despite high levels of DNA damage. Inhibition of polyamine synthesis or SMO could abrogate the development of this cell population that may represent precursors for neoplastic transformation.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center; Nashville, TN, USA.
authors.forename: Rupesh
authors.initials: R
authors.lastname: Chaturvedi
authors.forename: Thibaut
authors.initials: T
authors.lastname: de Sablet
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D004249:DNA Damage; D004847:Epithelial Cells / Q000201:enzymology / Q000502:physiology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology; D016480:Helicobacter pylori / Q000201:enzymology* / Q000472:pathogenicity*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000096:biosynthesis*; D013096:Spermine / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology*; D037521:Virulence Factors / Q000378:metabolism; D000097667:Polyamine Oxidase
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006861:Hydrogen Peroxide; D000587:Oxidoreductases Acting on CH-NH Group Donors; D013096:Spermine; D037521:Virulence Factors; D000097667:Polyamine Oxidase; C080866:cagA protein, Helicobacter pylori