Interactions between ovine cathepsin L, cystatin C and alpha 2-macroglobulin. Potential role in the genital tract.
The specific inhibitor of cysteine proteinases, cystatin C, was purified from ram rete testis fluid and the conditioned medium of Sertoli cells. This molecule associated with sheep liver cathepsin L at one of the fastest rates ever described for a proteinase/inhibitor interaction (1.75 +/- 0.20 x 10(8) M-1.s-1). But the association rate constant for the interaction of cathepsin L with alpha 2-macroglobulin, a non-specific inhibitor of proteinases, was also extremely high (8.8 +/- 0.75 x 10(6) M-1.s-1). Cathepsin L complexed with alpha 2-macroglobulin was protected from inhibition by type 2 and type 3 cystatins. The data indicate that cystatin C is the most potent inhibitor of cathepsin L in mammalian male genital tract fluids, whereas alpha 2-macroglobulin may act as a terminal acceptor of this enzyme. These inhibitors could therefore inhibit the activated form of procathepsin L which may appear during the complex process of spermatozoa production and maturation in the testis and epididymis.
Peloille
S
S
Laboratoire d'Enzymologie et Chimie des Protéines, EP CNRS 117, Université François Rabelais, Tours, France.
Esnard
A
A
Dacheux
J L
JL
Guillou
F
F
Gauthier
F
F
Esnard
F
F
D000595:Amino Acid Sequence; D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D055316:Cystatin C; D015891:Cystatins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004357:Drug Synergism; D010450:Endopeptidases; D008297:Male; D008969:Molecular Sequence Data; D012152:Rete Testis / Q000187:drug effects / Q000378:metabolism*; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D012756:Sheep; D000511:alpha-Macroglobulins / Q000378:metabolism* / Q000494:pharmacology
D055316:Cystatin C; D015891:Cystatins; D000511:alpha-Macroglobulins; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L