Ureases display biological effects independent of enzymatic activity: is there a connection to diseases caused by urease-producing bacteria?
Ureases are enzymes from plants, fungi and bacteria that catalyze the hydrolysis of urea to form ammonia and carbon dioxide. While fungal and plant ureases are homo-oligomers of 90-kDa subunits, bacterial ureases are multimers of two or three subunit complexes. We showed that some isoforms of jack bean urease, canatoxin and the classical urease, bind to glycoconjugates and induce platelet aggregation. Canatoxin also promotes release of histamine from mast cells, insulin from pancreatic cells and neurotransmitters from brain synaptosomes. In vivo it induces rat paw edema and neutrophil chemotaxis. These effects are independent of ureolytic activity and require activation of eicosanoid metabolism and calcium channels. Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach mucosa, causes gastric ulcers and cancer by a mechanism that is not understood. H. pylori produces factors that damage gastric epithelial cells, such as the vacuolating cytotoxin VacA, the cytotoxin-associated protein CagA, and a urease (up to 10% of bacterial protein) that neutralizes the acidic medium permitting its survival in the stomach. H. pylori whole cells or extracts of its water-soluble proteins promote inflammation, activate neutrophils and induce the release of cytokines. In this paper we review data from the literature suggesting that H. pylori urease displays many of the biological activities observed for jack bean ureases and show that bacterial ureases have a secretagogue effect modulated by eicosanoid metabolites through lipoxygenase pathways. These findings could be relevant to the elucidation of the role of urease in the pathogenesis of the gastrointestinal disease caused by H. pylori.
Olivera-Severo
D
D
Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
Wassermann
G E
GE
Carlini
C R
CR
D000818:Animals; D032449:Canavalia / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004378:Duodenal Diseases / Q000378:metabolism / Q000382:microbiology; D015777:Eicosanoids / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology*; D016480:Helicobacter pylori / Q000201:enzymology* / Q000472:pathogenicity; D006801:Humans; D010940:Plant Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D013272:Stomach Diseases / Q000378:metabolism / Q000382:microbiology; D014118:Toxins, Biological / Q000096:biosynthesis* / Q000494:pharmacology; D014510:Urease / Q000096:biosynthesis*
D015777:Eicosanoids; D010940:Plant Proteins; D014118:Toxins, Biological; C032815:canatoxin; D014510:Urease