Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa.
Protein C inhibitor (PCI) is synthesized by cells throughout the male reproductive tract and is present in high concentrations (220 micrograms/ml) in seminal plasma. Seminal plasma as well as the acrosome of spermatozoa are rich in possible target proteases for PCI. We analyzed the interaction of PCI with acrosin, a serine protease stored in its zymogen form in the acrosome of spermatozoa. Purified human PCI inhibited the amidolytic activity of purified boar acrosin with an apparent second-order rate constant of 3.7 x 10(4) M-1.s-1. Inhibition was paralleled by the degradation of PCI from its 57- to its 54-kDa form. Human PCI also inhibited the amidolytic activity of activated human sperm extracts and formed complexes with acrosin as determined by an enzyme-linked immunosorbent assay. Immunocytochemistry revealed that morphologically abnormal spermatozoa stained for PCI antigen, whereas morphologically normal spermatozoa were negative. In immunoelectron microscopy, PCI was exclusively localized in the immediate vicinity of disrupted acrosomal membranes of sperm heads. These data suggest that PCI might function as a scavenger of prematurely activated acrosin, thereby protecting intact surrounding cells and seminal plasma proteins from possible proteolytic damage.
Zheng
X
X
Department of Medical Physiology, University of Vienna, Austria.
Geiger
M
M
Ecke
S
S
Bielek
E
E
Donner
P
P
Eberspächer
U
U
Schleuning
W D
WD
Binder
B R
BR
D000176:Acrosin / Q000037:antagonists & inhibitors*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D016253:Microscopy, Immunoelectron; D018046:Protein C Inhibitor / Q000378:metabolism* / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism* / Q000648:ultrastructure; D013194:Staining and Labeling; D013552:Swine; D014018:Tissue Distribution
D018046:Protein C Inhibitor; D000176:Acrosin