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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

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

Grazyna Bras, Oliwia Bochenska, Maria Rapala-Kozik, Ibeth Guevara-Lora, Alexander Faussner, Wojciech Kamysz, Andrzej Kozik

Peptides. 2013 Oct;48:114-23.

PMID: 23954712

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP165174607	Met-Lys-[Ser2, Arg3, Pro5, Arg8]-Bradykinin		165174-60-7	Price

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