Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of DNA homology to bee venom hyaluronidase, it was recently suggested that the GPI-linked mammalian sperm antigen, PH-20, may function as a cell surface hyaluronidase [Gmachl, M., & Kreil, G. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 3569-3573]. We have quantified the activity of the soluble acrosomal hyaluronidase of mouse sperm and further demonstrate the existence of a membrane-bound hyaluronidase, detected on both acrosome-intact and acrosome-reacted mouse sperm, distinct from the soluble form of the enzyme. The membrane-bound hyaluronidase was specifically released by PI-PLC, indicating that it is GPI linked. Acrosome-intact and acrosome-reacted sperm released several polypeptides (68, 44, 39, 34, 17, and 15 kDa) when treated with PI-PLC. In addition, GPI-linked polypeptides unique to acrosome-intact or to acrosome-reacted sperm were identified. Fractionation of the PI-PLC-released components from acrosome-reacted sperm using size exclusion chromatography revealed a single peak of hyaluronidase activity which comigrates with a 68 kDa GPI-linked protein present in these fractions. Taken together, these data demonstrate the existence of at least two isoforms of hyaluronidase: a soluble form within the acrosomal vesicle which is released during acrosomal exocytosis and a GPI-linked form which is present on the surface of both acrosome-intact and acrosome-reacted sperm. Both forms may be necessary for successful penetration of the extracellular vestments that surround the egg prior to fertilization.
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PMID:Biochemical characterization of a glycosylphosphatidylinositol-linked hyaluronidase on mouse sperm. 779 89

In mice bearing the Rb(6.16) or Rb(6.15) Robertsonian translocation (Rb), sperm dysfunction associated with the Rbs has been shown to lead to transmission ratio distortions (TRDs) in heterozygotes. The severity of the TRDs is directly related to the severity in the alteration of expression of the gene for the Sperm Adhesion Molecule 1 (Spam1), which maps to proximal mouse Chromosome 6 (Chr 6) near the translocation junction and encodes a sperm antigen with hyaluronidase activity. Here we demonstrate that there is a significantly reduced fertility in the Rb homozygotes (P < 0.001), based on litter size; and that with the Sperm Select Penetration assay Rb-bearing sperm have significantly decreased (P < 0.02-0.001) rates of penetration of hyaluronic acid. Catalytic kinetics studies indicate that reduced Spam1 (PH-20) hyaluronidase activity in the Rb(6.15) mice results from a qualitative defect, while for Rb(6.16) with the greater TRD both a qualitative and a quantitative deficiency (confirmed by Western analysis) of Spam1 exist. Six point mutations were shown to be clustered in the Spam1 hyaluronic acid-binding domain in Rb(6.15). For Rb(6.16) which has a gross genomic alteration at the Spam1 locus, 11 point mutations are scattered in the 5' and 3' UTRs and the coding region, where one leads to the replacement of a conserved residue. Entrapment of spontaneous Spam1 mutations, owing to recombination suppression near the Rb junctions, is proposed as the major underlying defect of the sperm dysfunction.
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PMID:Spam1 (PH-20) mutations and sperm dysfunction in mice with the Rb(6.16) or Rb(6.15) translocation. 1184 84

A widely conserved sperm antigen, the sperm adhesion molecule 1 (SPAM1 or PH-20) is a glycosylphosphatidyl inositol-linked protein with multiple roles in mammalian fertilization. It has been shown to be dually expressed in testis and epididymis and this is conserved in the four species (mouse, rat, macaques, humans) that have been studied to date. Here, we report Spam1 RNA and protein expression in the murine vas deferens and efferent ducts. In situ hybridization and immunohistochemistry indicate that transcript and protein are distributed in the nonciliated epithelial cells and that the efferent ducts have the most intense staining of all three regions of the excurrent ducts. Spam1 products were also present in the accessory organs, the prostate, and seminal vesicles and its fluid. Using hyaluronic acid substrate gel electrophoresis, hyaluronidase activity at pH 7.0 was detected in the vas deferens but was absent from the efferent ducts, the prostate, and the seminal vesicles/fluid. This suggests that Spam1 may play a nonenzymatic role in these organs. In the efferent ducts, where Spam1 is enriched in the apical (but not basolateral) membrane of nonciliated cells, it is likely to play a role in sperm concentration, which is the established function of that organ.
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PMID:Spam1 (PH-20) expression in the extratesticular duct and accessory organs of the mouse: a possible role in sperm fluid reabsorption. 1517 39

The Sperm Adhesion Molecule1 (SPAM1) is the most widely conserved sperm antigen with important roles in mammalian fertilization. Light and electron microscopy were used to localize, by in situ hybridization, the cellular and subcellular sites of Spam1 mRNA in the murine testis. Transcripts were first detected in step 3 round spermatids, gradually increased until step 8 and abruptly decreased between steps 9-11. They were predominantly localized near the ER and were not dispersed throughout the cytoplasm. Immunohistochemistry revealed that Spam1 is present on both the head and tail of sperm in the seminiferous tubules, and provided support for transcriptional regulation of its transcript. Immunocytochemistry confirmed the location of Spam1 on the tail of testicular sperm and demonstrated that it is localized to both the principal piece and the midpiece. Spam1 on epididymal sperm is localized to the midpiece of the tail and changes from a uniform distribution on the head in the caput to a regionalized pattern, first on the posterior and then on the anterior head, in caudal sperm. Spam1 on the surface of caudal sperm was shown to mediate the increase in acrosome reactions induced by the synergistic effects of HA and progesterone, as confirmed in sperm from the Rb(6.16) translocation-bearing mice which are Spam1 mutants. The similar response of human and mouse sperm to these agonists of the acrosome reaction, underscores the usefulness of the mouse as a model to study physiological aspects of SPAM1 in humans where, unlike the mouse, it is the only sperm hyaluronidase.
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PMID:Cytoplasmic localization during testicular biogenesis of the murine mRNA for Spam1 (PH-20), a protein involved in acrosomal exocytosis. 1545 44

The most widely conserved mammalian sperm antigen is sperm adhesion molecule 1, SPAM1/PH-20, which is also the major testicular hyaluronidase. This multifunctional glycosyl phosphatidylinositol (GPI)-linked protein plays several roles in fertilization and is encoded by a gene that resides among hyaluronidase family members in a cluster on human 7q31/mouse 6A2. In the human cluster, SPAM1 is the only functional hyaluronidase and of all six hyaluronidases in the genome it is the best characterized, both structurally and functionally. While SPAM1 transcripts are abundantly expressed only in the testis, specifically in spermatids, the RNA and protein are present in the male reproductive tract and accessory organs and in the female tract of mice. Our investigation of the post-testicular expression of SPAM1 shows that the protein is widely expressed in the epididymis. Like testicular SPAM1, epididymal SPAM1 (ES) has hyaluronidase activity and is conserved in at least five species (mouse, rat, bull, macaque, and human) all of which have putative androgen response elements in the gene promoters, consistent with androgen regulation. Testicular lumicrine factors have also been implicated in ES regulation. Based on regional expression, the protein is likely to play a role in both sperm maturation and storage. A minor secretory glycoprotein, ES is present in the epididymal luminal fluid in both a soluble and insoluble form (epididymosomes), with the latter having an intact lipid anchor. Genetic approaches have provided evidence for sperm uptake of ES in vivo, and in vitro uptake has been demonstrated with the use of Spam1 null mice. In vitro acquisition of ES on the sperm surface results in a pattern that mimics the wild-type distribution. More importantly it significantly increases the ability of null sperm to penetrate the cumulus of oocytes via hyaluronidase activity, directly relating ES uptake with fertilizing ability and indicating that ES is a marker of sperm maturation.
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PMID:Epididymal SPAM1 and its impact on sperm function. 1642 Sep 70

Sperm uptake of epididymal sperm adhesion molecule 1 (SPAM1) in vitro has recently been shown to be a marker of sperm maturation, since acquisition of this surface hyaluronidase increases cumulus dispersal efficiency. Here, we demonstrate that this glycosyl phosphatidylinositol-linked sperm antigen, previously shown to be expressed during estrous in the female reproductive tract, is secreted in the uterine and oviductal fluids (ULF and OF respectively) in a 67 kDa form, which can bind to sperm. We show that it can be acquired by caudal sperm from Spam1 null, Spam1-deficient mutant, and wild-type (WT) mice in vitro during incubation in ULF or OF at 37 degrees C, as detected by immunocytochemistry and flow cytometry. SPAM1 binding after ULF incubation was localized predominantly to the acrosome and the mid-piece of the flagella of Spam1 null sperm in a pattern identical to that of WT sperm. After ULF incubation, WT sperm demonstrated a significantly (P<0.001) enhanced hyaluronic acid-binding ability, and the involvement of SPAM1 in this activity was shown by a significant (P<0.001) decrease in binding when sperm were exposed to SPAM1 antiserum-inhibited ULF. Importantly, when Spam1 null sperm were exposed to ULF with SPAM1 accessible (in the presence of pre-immune serum) or inaccessible (in the presence of SPAM1 antiserum) for uptake, there was a significant difference in cumulus dispersal efficiency. Taken together, these results suggest that in the sperm surface remodeling that occurs prior to and during capacitation, the fertilizing competence of sperm is increased via acquisition of SPAM1, and likely other hyaluronidases, from the female tract.
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PMID:Murine SPAM1 is secreted by the estrous uterus and oviduct in a form that can bind to sperm during capacitation: acquisition enhances hyaluronic acid-binding ability and cumulus dispersal efficiency. 1829 22

Sperm proteins are known to be associated with normal fertilization as auto- or iso-antibodies to these proteins may cause infertility. Therefore, sperm proteins have been considered to be the potential candidate for the development of antifertility vaccine. Some of the sperm proteins proved to be promising antigens for contraceptive vaccine includes lactate dehydrogenase (LDH-C4), protein hyaluronidase (PH-20), and Eppin. Immunization with LDH-C4 reduced fertility in female baboons but not in female cynomolgus macaques. Active immunization with PH-20 resulted in 100 per cent inhibition of fertility in male guinea pigs but it induced autoimmune orchitis. Immunization with Eppin elicited high antibody titres in 78 per cent of immunized monkeys and induced infertility but the immunopathological effect of immunization was not examined. Human sperm antigen (80 kDa HSA) is a sperm specific, highly immunogenic and conserved sperm protein. Active immunization with 80 kDa HSA induced immunological infertility in male and female rats. Partial N-terminal amino acid sequence of 80 kDa HSA (Peptide NT) and its peptides (Peptides 1, 2, 3 and 4) obtained by enzymatic digestion did not show homology with any of the known proteins in gene bank. Peptides NT, 1, 2 and 4 were found to mimic immunobiological activity of native protein. Passive administration of antibodies to peptides NT, 1, 2 and 4 induced infertility in male and female rats and peptide 1 was found to be most effective in suppressing fertility. Active immunization with keyhole limpet haemocynin (KLH) conjugated synthetic peptide 1 impaired fertility in all the male rabbits and six of the seven male marmosets. The fertility was restored following decline in antibody titre. All these findings on 80 kDA HAS suggest that the synthetic Peptide-1 of 80 kDa HSA is the promising candidate for development of male contraceptive vaccine.
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PMID:Development of antifertility vaccine using sperm specific proteins. 2567 47