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)

Daily administration of 2g/kg/day di(2-ethylhexyl)phthalate (DEHP) to immature rats was found to cause testicular atrophy and reduce zinc concentration. Specific activities of testicular enzymes associated with postmeiotic spermatogenic cells, such as lactate dehydrogenase isozyme-X, hyaluronidase and sorbitol dehydrogenase, were lower than those of control by day 10, coincident with degeneration of spermatogenic cells. The specific activities of enzymes associated with premeiotic spermatogenic cells, Sertoli cells or interstitial cells (beta-glucuronidase, gamma-glutamyl transpeptidase and malate dehydrogenase) were higher than those of control by day 10. The specific activities of alcohol dehydrogenase and aldolase, zinc containing enzymes, increased after DEHP treatment in spite of the decrease in zinc concentration in the testis. In conclusion, changes in several testicular cell-specific enzymes appear to be useful biochemical markers of testicular injury induced by testicular toxicants such as DEHP. However, these changes occurred after or simultaneous with massive histological or morphological changes rather than prior to such changes.
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PMID:Testicular atrophy induced by di(2-ethylhexyl)phthalate: changes in histology, cell specific enzyme activities and zinc concentrations in rat testis. 288 30

To determine how hyaluronidase increases certain cancer cell sensitivity to tumor necrosis factor (TNF) cytotoxicity, we report here the isolation and characterization of a hyaluronidase-induced murine WW domain-containing oxidoreductase (WOX1). WOX1 is composed of two N-terminal WW domains, a nuclear localization sequence, and a C-terminal alcohol dehydrogenase (ADH) domain. WOX1 is mainly located in the mitochondria, and the mitochondrial targeting sequence was mapped within the ADH domain. Induction of mitochondrial permeability transition by TNF, staurosporine, and atractyloside resulted in WOX1 release from mitochondria and subsequent nuclear translocation. TNF-mediated WOX1 nuclear translocation occurred shortly after that of nuclear factor-kappaB nuclear translocation, whereas both were independent events. WOX1 enhanced TNF cytotoxicity in L929 cells via its WW and ADH domains as determined using stable cell transfectants. In parallel with this observation, WOX1 also enhanced TRADD (TNF receptor-associated death domain protein)-mediated cell death in transient expression experiments. Antisense expression of WOX1 raised TNF resistance in L929 cells. Enhancement of TNF cytotoxicity by WOX1 is due, in part, to its significant down-regulation of the apoptosis inhibitors Bcl-2 and Bcl-x(L) (>85%), but up-regulation of pro-apoptotic p53 ( approximately 200%) by the ADH domain. When overexpressed, the ADH domain mediated apoptosis, probably due to modulation of expression of these proteins. The WW domains failed to modulate the expression of these proteins, but sensitized COS-7 cells to TNF killing and mediated apoptosis in various cancer cells independently of caspases. Transient cotransfection of cells with both p53 and WOX1 induced apoptosis in a synergistic manner. WOX1 colocalizes with p53 in the cytosol and binds to the proline-rich region of p53 via its WW domains. Blocking of WOX1 expression by antisense mRNA abolished p53 apoptosis. Thus, WOX1 is a mitochondrial apoptogenic protein and an essential partner of p53 in cell death.
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PMID:Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity. 1105 90