Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acidic extracts of washed, ejaculated human spermatozoa contain, besides acrosin, two proteinase inhibitors, a trypsin-chymotrypsin (elastase) inhibitor (HUSI-I) and a trypsin-acrosin inhibitor (HUSI-II). Using the indirect immunofluorescence technique these inhibitors could be localized in the spermatozoa. Ejaculated spermatozoa were treated with monospecific antibodies raised in rabbits against HUSI-I and HUSI-II, respectively, and with fluorescein-labeled IgG from goat directed against the rabbit IgG. If acetone-fixed spermatozoa were used, fluorescence appeared only in a small ring near or at the equatorial segment of the spermatozoa. After prefixation of washed spermatozoa with 0.36% formaldehyde, however, distribution of both inhibitors in the region of the acrosomal caps could clearly be demonstrated. Present results suggest that they are attached at the plasma membrane. Obviously, in the case of human spermatozoa the inhibitors are relatively easily detached together with the membrane so that prefixation is necessary to achieve proper localization.
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PMID:Localization of seminal plasma proteinase inhibitors in human spermatozoa as revealed by the indirect immunofluorescence technique. 79 87

Human seminal plasma contains two acid-stable proteinase inhibitors, HUSI-II (Mr approximately 6500) and HUSI-I, (Mr approximately 11 000) with different inhibition specificities. The inhibitory activity of HUSI-II is strongly limited to trypsin and acrosin; both enzyme-inhibitor complexes are very stable (e.g. bovine trypsin-HUSI-II complex: Ki = 1 x 10(-10)M; human acrosin-HUSI-II complex: Ki = 2.7 x 10(-10)M). The inhibitor from human seminal plasma HUSI-II may therefore be seen as the natural antagonist of the sperm protease acrosin. In addition to pancreatic trypsin and alpha-chymotrypsin, HUSI-I forms strong complexes with neutral proteases of the lysosome-like granules from human granulocytes, for example, the elastase (Ki = 2.5 x 10(-9)M) and cathepsin G, the chymotrypsin like protease (Ki = 7 x 10(-8)M).
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PMID:Inhibitors of acrosin and granulocyte proteinases from human genital tract secretions. 99 78

Horse seminal plasma does not possess a proteinase inhibitor corresponding to human HUSI-I (human seminal plasma inhibitor). Instead a protein complex of high relative molecular mass (Mr) containing proteinase inhibitory activity was detected, which was called horse seminal plasma protein complex or HSPC. The compound had a broad enzyme-inhibiting spectrum. Its Mr was estimated to be 800 000 and it was composed of 7 different polypeptides with Mr values ranging from 11 000 to 30 000. Its carbohydrate content was between 3.5% and 5%. Despite the high molecular mass, the complex was soluble in diluted perchloric acid and did not lose its biological activity. The high recovery of seminal plasma protein (69%) after perchloric acid treatment, the unaltered immunoelectrophoretic precipitation pattern of the perchloric acid soluble part of seminal plasma, and the similarity of the polypeptide patterns of unfractionated seminal plasma and HSPC suggest that HSPC is one of the major components of horse seminal plasma. In addition to HSPC, horse seminal plasma contained a group of three electrophoretically distinguishable proteinase inhibitors, corresponding roughly to a Mr of 6500. They inhibited only trypsin. The similar Mr values and the identical narrow enzyme specificity suggest that they are isoinhibitors and may be analogues of human HUSI-II (human seminal plasma inhibitor). The lack of a HUSI-I analog in the horse is discussed in relation to a previously made observation that horse tracheobronchial fluid contains no detectable perchloric acid-soluble proteinase inhibitors.
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PMID:Proteinase inhibitors of horse seminal plasma. A high molecular mass, acid-soluble proteinase inhibitor. 299 13

Spermatogenesis is a complex process involving an intrinsic genetic program composed of germ cell-specific and -predominant genes. In this study, we investigated the mouse Spink2 (serine protease inhibitor Kazal-type 2) gene, which belongs to the SPINK family of proteins characterized by the presence of a Kazal-type serine protease inhibitor-pancreatic secretory trypsin inhibitor domain. We showed that recombinant mouse SPINK2 has trypsin-inhibitory activity. Distribution analyses revealed that Spink2 is transcribed strongly in the testis and weakly in the epididymis, but is not detected in other mouse tissues. Expression of Spink2 is specific to germ cells in the testis and is first evident at the pachytene spermatocyte stage. Immunoblot analyses demonstrated that SPINK2 protein is present in male germ cells at all developmental stages, including in testicular spermatogenic cells, testicular sperm, and mature sperm. To elucidate the functional role of SPINK2 in vivo, we generated mutant mice with diminished levels of SPINK2 using a gene trap mutagenesis approach. Mutant male mice exhibit significantly impaired fertility; further phenotypic analyses revealed that testicular integrity is disrupted, resulting in a reduction in sperm number. Moreover, we found that testes from mutant mice exhibit abnormal spermatogenesis and germ cell apoptosis accompanied by elevated serine protease activity. Our studies thus provide the first demonstration that SPINK2 is required for maintaining normal spermatogenesis and potentially regulates serine protease-mediated apoptosis in male germ cells.
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PMID:Impaired spermatogenesis and fertility in mice carrying a mutation in the Spink2 gene expressed predominantly in testes. 2170 36