Title of article :
Modulation of hypotensive effects of kinins by cathepsin K
Author/Authors :
F. Lecaille، نويسنده , , Fabien and Vandier، نويسنده , , Christophe and Godat، نويسنده , , Emmanuel and Hervé-Grépinet، نويسنده , , Virginie and Brِmme، نويسنده , , Dieter and Lalmanach، نويسنده , , Gilles، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2007
Abstract :
Kinins are pro-inflammatory peptides, which participate in the maintenance of cardiovascular homeostasis, and play a key role in numerous diseases, including lung fibrosis and hypertension. Evidence has been provided recently for the presence of alternative mechanisms of bradykinin generation and/or degradation. Here we showed that cathepsin K may act as a potent kinin-degrading enzyme in bloodstream. Contrary to cathepsin L, cathepsin K attenuates kallikrein-induced decrease of rat blood pressure, and reduces the hypotensive effect of bradykinin in a dose-dependant manner. Moreover, we identified, by engineering the S2 subsite of both recombinant enzymes, two critical residues involved respectively in the kininase activity of cathepsin K, i.e. Tyr67/Leu205, versus kininogenase activity of cathepsin L, i.e. Leu67/Ala205. In conclusion, according to its ability to modulate hypotensive effects of kinins, we propose that cathepsin K is a kininase of biological relevance, in complement of well-documented neutral endopeptidase or angiotensin-converting enzyme.
Keywords :
cysteine protease , Kininase , Kinin , cathepsin , peptidase
Journal title :
Archives of Biochemistry and Biophysics
Journal title :
Archives of Biochemistry and Biophysics