Cleavage of human big endothelin-1 by Candida albicans aspartic proteinase.
A Candida albicans aspartic proteinase (CAP), one of the secretory proteinases of Candida albicans, is thought to be a possible virulence factor in Candida albicans infection. Whereas endothelin-1 is found as an endothelium-derived strong vasoconstrictive peptide, it is known to have a role in the maintenance of vascular homeostasis and tissue survival. Endothelin-1 is generated from a precursor form of endothelin-1, the so-called big endothelin-1. It has recently been reported that cathepsin D, E and pepsin, which are aspartic proteinases, convert big endothelin-1 to endothelin-1. In this study, the relationship between CAP and big endothelin-1 was studied. High performance liquid chromatography analysis revealed that big endothelin-1 was cleaved into several amino acid sites by CAP, but endothelin-1 was not converted from big endothelin-1. CAP cleaved big endothelin-1 at different sites when compared with that of other known aspartic proteinases, and it suppressed endothelin-1 production through the degradation of big endothelin-1. CAP may break homeostatic mechanism of endothelin-1 in Candida albicans infectious lesions.
Tsushima
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Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan.
Mine
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H
D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002176:Candida albicans / Q000201:enzymology* / Q000472:pathogenicity; D002402:Cathepsin D / Q000378:metabolism; D020059:Cathepsin E; D002403:Cathepsins / Q000378:metabolism; D002853:Chromatography, Liquid; D019332:Endothelin-1; D016232:Endothelins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010434:Pepsin A / Q000378:metabolism; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism*; D014774:Virulence
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D002403:Cathepsins; D016282:Aspartic Acid Endopeptidases; D010434:Pepsin A; D020059:Cathepsin E; D002402:Cathepsin D