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

Immunointerruption of pregnancy consists of preventing pregnancy or terminating it at an early stage through antibodies. The antibodies may be obtained after administration of vaccine to induce their formation through active immunization, or by direct injection through passive immunization. Antigens that could potentially be used are found in sperm, the zona pellucida, and reproductive hormones, especially the chorionic gonadotropins. The sperm antigens are basically enzymes such as hyaluronidase and accrosine. 3 glucoproteins have been identified in the zona pellucida of mice and pigs. In vitro studies have shown that fertilization can be prevented if eggs are exposed to antizona-pellucida antibodies along with sperm. Active immunization could give longer term results, but ovarian function could also be affected if the antigens weren't purified. Much research has been devoted to identifying human embryonic antigens through analysis of the proteins of the cells of embryonic teratocarcinoma. Among placental antigens, the glucoprotein SP1 synthesized by the trophoblast is under study. Anti-SP1 antibodies appear to cause abortion in monkeys, but knowledge of these antigens is still fragmentary. Various reproductive hormones have been studied, but too many undesirable effects could result from the use of luteinizing hormone, luteinizing hormone releasing hormone, follicle stimulation hormone, or steroids. Human chorionic gonadotropin (hCG), however, is more promising. It is a glucoprotein formed of alpha and beta subunits, both of which are needed for hCG to interact with its receptor. The alpha subunit has the same sequence as that of other hormones of the same species, but the beta subunit is specific to each hormone. Studies are underway to determine the site of amino acids and peptide sequences capable of inducing an anti-hCG response which would inactivate the biological activity of hCG. Different teams have used synthetic peptides analogous to sequences of beta-hCG or fragments obtained by enzymatic cleavage of natural hCG to block pregnancy in rats and baboons. The presence of antibodies can block pregnancy without disturbing ovulation or modifying menstrual regularity. No toxic or secondary effect has been observed in animals. A multicenter phase 1 test using beta-hCG coupled with tetanus antitoxin caused almost all the women participating to develop antibeta-hCG and antitetanus anatoxin antibodies, but titres of antibodies varied greatly between different women, required 5-6 months to develop, and declined rapidly thereafter. Several pregnancies were observed, especially in women with low titres of antibodies. The approach of passive immunization through direct injection of antibodies has met with numerous obstacles, including lack of success in producing human monoclonal antibodies. Although a 2nd generation of vaccines in under study, the potential role of immunointerruption of pregnancy in fertility regulation remains to be clarified.
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PMID:[Regulation of fertility by anti-hCG vaccines]. 1228 Dec 42

HYAL-1 (hyaluronoglucosaminidase-1) belongs to the hyaluronidase family of enzymes that degrade hyaluronic acid. HYAL-1 is a marker for cancer diagnosis and a molecular determinant of tumor growth, invasion, and angiogenesis. The regulation of HYAL-1 expression is unknown. Real time reverse transcription-PCR using 11 bladder and prostate cancer cells and 69 bladder tissues showed that HYAL-1 mRNA levels are elevated 10-30-fold in cells/tissues that express high hyaluronidase activity. Although multiple transcription start sites (TSS) for HYAL-1 mRNA were detected in various tissues, the major TSS in many tissues, including bladder and prostate, was at nucleotide 27274 in the cosmid clone LUCA13 (AC002455). By analyzing the 1532 base sequence 5' to this TSS, using cloning and luciferase reporter assays, we identified a TACAAA sequence at position -31 and the minimal promoter region between nucleotides -93 and -38. Mutational analysis identified that nucleotides -73 to -50 (which include overlapping binding consensus sites for SP1, Egr-1, and AP-2), bases C(-71) and C(-59), and an NFkappaB-binding site (at position -15) are necessary for promoter activity. The chromatin immunoprecipitation assay identified that Egr-1, AP-2, and NFkappaB bind to the promoter in HYAL-1-expressing cells, whereas SP1 binds to the promoter in non-HYAL-1-expressing cells. 5-Aza-2'-deoxycytidine treatment, bisulfite DNA sequencing, and methylation-specific PCR revealed that HYAL-1 expression is regulated by methylation at C(-71) and C(-59); both Cs are part of the SP1/Egr-1-binding sites. Thus, HYAL-1 expression is epigenetically regulated by the binding of different transcription factors to the methylated and unmethylated HYAL-1 promoter.
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PMID:Epigenetic regulation of HYAL-1 hyaluronidase expression. identification of HYAL-1 promoter. 1871 11