Release of biologically active kinin peptides, Met-Lys-bradykinin and Leu-Met-Lys-bradykinin from human kininogens by two major secreted aspartic proteases of Candida parapsilosis.

Abstract

In terms of infection incidence, the yeast Candida parapsilosis is the second after Candida albicans as causative agent of candidiases in humans. The major virulence factors of C. parapsilosis are secreted aspartic proteases (SAPPs) which help the pathogen to disseminate, acquire nutrients and dysregulate the mechanisms of innate immunity of the host. In the current work we characterized the action of two major extracellular proteases of C. parapsilosis, SAPP1 and SAPP2, on human kininogens, proteinaceous precursors of vasoactive and proinflammatory bradykinin-related peptides, collectively called the kinins. The kininogens, preferably the form with lower molecular mass, were effectively cleaved by SAPPs, with the release of two uncommon kinins, Met-Lys-bradykinin and Leu-Met-Lys-bradykinin. While optimal at acidic pH (4-5), the kinin release yield was only 2-3-fold lower at neutral pH. These peptides were able to interact with cellular kinin receptors of B2 subtype and to stimulate the human endothelial cells HMEC-1 to increased secretion of proinflammatory interleukins (ILs), IL-1β and IL-6. The analysis of the stability of SAPP-generated kinins in plasma suggested that they are biologically equivalent to bradykinin, the best agonist of B2 receptor subtype and can be quickly converted to des-Arg(9)-bradykinin, the agonist of inflammation-inducible B1 receptors.

• Authors: Grazyna Bras, Oliwia Bochenska, Maria Rapala-Kozik, Ibeth Guevara-Lora, Alexander Faussner, Wojciech Kamysz, Andrzej Kozik
• Journal: Peptides (Peptides) Vol. 48 Pg. 114-23 (Oct 2013) ISSN: 1873-5169 [Electronic] United States
• PMID: 23954712 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Fungal Proteins
• Kininogens
• Oligopeptides
• Peptides
• bradykinin potentiating factors
• bradykinin, Met-Lys-
• Aspartic Acid Proteases
• Aspartic Acid Endopeptidases
• SAPP1 protein, Candida parapsilosis
• Bradykinin

Topics

• Aspartic Acid Endopeptidases (metabolism)
• Aspartic Acid Proteases
• Bradykinin (analogs & derivatives, chemistry, metabolism)
• Candida (enzymology, pathogenicity)
• Candidiasis (enzymology, microbiology, pathology)
• Endothelial Cells
• Fungal Proteins (metabolism)
• Humans
• Kininogens (chemistry, metabolism)
• Oligopeptides
• Peptides (chemistry, metabolism)