RSS-Feed abonnieren
DOI: 10.1055/s-2006-958461
The Interaction among Protein C Inhibitor, Prostate-Specific Antigen, and the Semenogelin System
Publikationsverlauf
Publikationsdatum:
29. Januar 2007 (online)

ABSTRACT
The kallikrein-like serine protease, prostate-specific antigen (PSA), is mixed in human seminal plasma with its protein substrates semenogelin (Sg) -I, Sg-II, and protein C inhibitor (PCI), which are produced in seminal vesicles. In the seminal plasma, PSA degrades Sg-I, and Sg-II, which are major components in insoluble coagula, and PCI inhibits PSA by forming a PSA-PCI complex. Digestion of seminal coagula with PSA releases PCI and PSA-PCI complex from the coagula into a soluble phase, suggesting the presence of active PCI within the coagula. PCI forms a ternary complex with PSA and Sg-II in the seminal plasma. The binding of Sg-II to PSA and PCI is influenced by pH, ionic strength, heparin, negatively charged dextran sulfate, divalent cations, and particularly by Zn2 +. These observations suggest that binding of PCI to Sg in seminal vesicles regulates the PSA-catalyzed degradation of Sg in seminal plasma; the complex formation among PCI, PSA, and Sg is modulated by several factors in seminal plasma.
KEYWORDS
Protein C inhibitor - prostate-specific antigen - semenogelins - seminal plasma - male reproduction
REFERENCES
- 1 Suzuki K, Deyashiki Y, Nishioka J et al.. Characterization of a cDNA for human protein C inhibitor: a new member of the plasma serine protease inhibitor superfamily. J Biol Chem. 1987; 262 611-616
- 2 Marlar R A, Griffin J H. Deficiency of protein C inhibitor in combined factor V/VIII deficiency disease. J Clin Invest. 1980; 66 1186-1189
- 3 Suzuki K, Nishioka J, Hashimoto S. Protein C inhibitor. Purification from human plasma and characterization. J Biol Chem. 1983; 258 163-168
- 4 Suzuki K, Nishioka J, Kusumoto H et al.. Mechanism of inhibition of activated protein C by protein C inhibitor. J Biochem (Tokyo). 1984; 95 187-195
- 5 Rezaie A R, Cooper S T, Church F C et al.. Protein C inhibitor is a potent inhibitor of the thrombin-thrombomodulin complex. J Biol Chem. 1995; 270 25336-25339
- 6 Meijers J CM, Kanters D H, Vlooswijk R A et al.. Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor. Biochemistry. 1988; 27 4231-4237
- 7 Stief T W, Radtke K P, Heimburger N. Inhibition of urokinase by protein C-inhibitor (PCI). Evidence for identity of PCI and plasminogen activator inhibitor 3. Biol Chem Hoppe Seyler. 1987; 368 1427-1433
- 8 Nishioka J, Ning M, Hayashi T, Suzuki K. Protein C inhibitor secreted from activated platelets efficiently inhibits activated protein C on phosphatidylethanolamine of platelet membrane and microvesicles. J Biol Chem. 1998; 273 11281-11287
- 9 Laurell M, Christensson A, Abrahamsson P A et al.. Protein C inhibitor in human body fluids: seminal plasma is rich in inhibitor antigen deriving from cells throughout the male reproductive system. J Clin Invest. 1992; 89 1094-1101
- 10 Moore A, Penford L M, Johnson J L et al.. Human sperm-egg binding is inhibited by peptides corresponding to core region of an acrosomal serine protease inhibitor. Mol Reprod Dev. 1993; 34 280-291
- 11 Hermans J M, Jones R, Stone S R. Rapid inhibition of the sperm protease acrosin by protein C inhibitor. Biochemistry. 1994; 33 5440-5444
- 12 Lilja H. A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest. 1985; 76 1899-1903
- 13 Christensson A, Lilja H. Complex formation between protein C inhibitor and prostate-specific antigen in vitro and in human semen. Eur J Biochem. 1994; 220 45-53
- 14 Wakita T, Hayashi T, Yuasa H et al.. Molecular cloning, tissue distribution and androgen regulation of rat protein C inhibitor. FEBS Lett. 1998; 429 263-268
- 15 Rollini P, Fournier R E. A 370-kb cosmid contig of the serpin gene cluster on human chromosome 14q32.1: molecular linkage of the genes encoding alpha 1- antichymotrypsin, protein C inhibitor, kallistatin, alpha 1-antitrypsin, and corticosteroid-binding globulin. Genomics. 1997; 46 409-415
- 16 Hayashi T, Usui T, Nishioka J et al.. Regulation of the human protein C inhibitor gene expression in HepG2 cells: role of Sp1 and AP2. Biochem J. 1998; 332 573-578
- 17 Hayashi T, Kume M, Nishioka J et al.. Characterization of mice transgenic for a human protein C inhibitor gene, useful as in vivo models for the evaluation of the therapeutic effects of human activated protein C. J Thromb Haemost. 2004; 2 949-961
- 18 Lovgren J, Airas K, Lilja H. Enzymatic action of human glandular kallikrein 2 (hK2). Substrate specificity and regulation by Zn2+ and extracellular protease inhibitors. Eur J Biochem. 1999; 262 781-789
- 19 Malm J, Hellman J, Hogg P et al.. Enzymatic action of prostate-specific antigen (PSA or hK3): substrate specificity and regulation by Zn(2 + ), a tight-binding inhibitor. Prostate. 2000; 45 132-139
- 20 Lundwall A, Lilja H. Molecular cloning of human prostate specific antigen cDNA. FEBS Lett. 1987; 214 317-322
- 21 Sutherland G R, Baker E, Hyland V J et al.. Human prostate-specific antigen (APS) is a member of the glandular kallikrein gene family at 19q13. Cytogenet Cell Genet. 1988; 48 205-207
- 22 Cleutjens K BJM, van Eekelen C CEM, van der Korput H AGM et al.. Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J Biol Chem. 1996; 271 6379-6388
- 23 Stamey T A, Yang N, Hay A R et al.. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med. 1987; 317 909-916
- 24 Lilja H, Lundwall A. Molecular cloning of epididymal and seminal vesicular transcripts encoding a semenogelin-related protein. Proc Natl Acad Sci USA. 1992; 89 4559-4563
- 25 Bjartell A, Malm J, Moller C et al.. Distribution and tissue expression of semenogelin I and II in man as demonstrated by in situ hybridization and immunocytochemistry. J Androl. 1996; 17 17-26
- 26 Lilja H, Abrahamsson P A, Lundwall A. Semenogelin, the predominant protein in human semen: primary structure and identification of closely related proteins in the male accessory sex glands and on the spermatozoa. J Biol Chem. 1989; 264 1894-1900
- 27 Jonsson M, Linse S, Frohm B et al.. Semenogelins I and II bind zinc and regulate the activity of prostate-specific antigen. Biochem J. 2005; 387 447-453
- 28 Laurell M, Christensson A, Abrahamsson P A et al.. Protein C inhibitor in human body fluids. Seminal plasma is rich in inhibitor antigen deriving from cells throughout the male reproductive system. J Clin Invest. 1992; 89 1094-1101
- 29 He S, Lin Y L, Liu Y X. Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility. Mol Hum Reprod. 1999; 5 513-519
- 30 Kise H, Nishioka J, Satoh K et al.. Measurement of protein C inhibitor in seminal plasma is useful for detecting agenesis of seminal vesicles or the vas deferens. J Androl. 2000; 21 207-212
- 31 Espana F, Fink E, Sanchez-Cuenca J et al.. Complexes of tissue kallikrein with protein C inhibitor in human semen and urine. Eur J Biochem. 1995; 234 641-649
- 32 Lilja H, Lundwall A. Molecular cloning of epidermal and seminal vesicular transcripts encoding a semenogelin-related protein. Proc Natl Acad Sci USA. 1992; 89 4559-4563
- 33 Christensson A, Lilja H. Complex formation between protein C inhibitor and prostate-specific antigen in vitro and in human semen. Eur J Biochem. 1994; 220 45-53
- 34 Kise H, Nishioka J, Kawamura J et al.. Characterization of semenogelin II and its molecular interaction with prostate-specific antigen and protein C inhibitor. Eur J Biochem. 1996; 238 88-96
- 35 de Lamirande E, Yoshida K, Yoshiike T M et al.. Semenogelin, the main protein of semen coagulum, inhibits human sperm capacitation by interfering with the superoxide anion generated during this process. J Androl. 2001; 22 672-679
- 36 Wakita T, Hayashi T, Yuasa H et al.. Molecular cloning, tissue distribution and androgen regulation of rat protein C inhibitor. FEBS Lett. 1998; 429 263-268
- 37 Moore A, Penfold L M, Johnson J L et al.. Human sperm-egg binding is inhibited by peptides corresponding to core region of an acrosomal serine protease inhibitor. Mol Reprod Dev. 1993; 34 280-291
- 38 Hermans J M, Jones R, Stone S R. Rapid inhibition of the sperm protease acrosin by protein C inhibitor. Biochemistry. 1994; 33 5440-5444
- 39 Zheng X, Geiger M, Ecke S et al.. Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa. Am J Physiol. 1994; 267 C466-C472
- 40 Elisen M G, van Kooij R J, Nolte M A et al.. Protein C inhibitor may modulate human sperm-oocyte interactions. Biol Reprod. 1998; 58 670-677
- 41 Espana F, Sanchez-Cuenca J, Fernandez P J et al.. Inhibition of human sperm-zona-free hamster oocyte binding and penetration by protein C inhibitor. Andrologia. 1999; 31 217-223
Professor Koji SuzukiPh.D.
Mie University Graduate School of Medicine
Edobashi 2-174, Tsu-city, Mie, 514-8507, Japan
eMail: suzuki@doc.medic.mie-u.ac.jp