title: Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg(9)-Met-Lys-bradykinin.
abstract: Bradykinin-related peptides, universal mediators of inflammation collectively referred to as the kinins, are often produced in excessive amounts during microbial infections. We have recently shown that the yeast Candida albicans, the major fungal pathogen to humans, can exploit two mechanisms to enhance kinin levels at the sites of candidial infection, one depending on adsorption and activation of the endogenous kinin-generating system of the host on the fungal cell wall and the other relying on cleavage of kinin precursors, the kininogens, by pathogen-secreted proteases. This work aimed at assigning this kininogenase activity to the major secreted aspartic protease of C. albicans (SAP2). The purified SAP2 was shown to cleave human kininogens, preferably the low molecular mass form (LK) and optimally in an acidic environment (pH 3.5-4.0), and to produce two kinins, Met-Lys-bradykinin and its derivative, [Hydroxyproline(3)]-Met-Lys-bradykinin, both of which are capable of interacting with cellular bradykinin receptors of the B2 subtype. Additionally, albeit with a lower yield, des-Arg(9)-Met-Lys-bradykinin, an effective agonist of B1-subtype receptors, was released. The pathophysiological potential of these kinins and des-Arg-kinin was also proven by presenting their ability to stimulate human promonocytic cells U937 to release proinflammatory interleukin 1β (IL-1β) and IL-6.
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Bras
authors.forename: Oliwia
authors.initials: O
authors.lastname: Bochenska
authors.forename: Maria
authors.initials: M
authors.lastname: Rapala-Kozik
authors.forename: Ibeth
authors.initials: I
authors.lastname: Guevara-Lora
authors.forename: Alexander
authors.initials: A
authors.lastname: Faussner
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kozik
mesh_terms: D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000276:immunology* / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002176:Candida albicans / Q000201:enzymology / Q000276:immunology*; D002177:Candidiasis / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D005656:Fungal Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007704:Kininogens / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D018002:Receptors, Bradykinin / Q000276:immunology
chemical_list: D005656:Fungal Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D007704:Kininogens; D018002:Receptors, Bradykinin; C018103:bradykinin, Met-Lys-; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida; D001920:Bradykinin