Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyaluronidase activity was detected and partially characterized in salivary gland extracts of females of six sand fly species. In Phlebotomus papatasi and Lutzomyia longipalpis the enzyme was active over a broad pH range; the pH optimum was 5.0. Besides high cleaving activity towards hyaluronic acid, it hydrolyzed chondroitin sulfates A and C. Hyaluronidases of various sand fly species differed in structure and sensitivity to reducing conditions. In the subgenera Phlebotomus (P. papatasi and P. duboscqi) and Adlerius (P. halepensis) the predominant active form of the enzyme was monomeric with the same apparent molecular weight under nonreducing and reducing conditions (around 65 kDa for P. papatasi and P. duboscqi and 110 kDa for P. halepensis). In P. sergenti the enzyme occurred as a putative homodimer but remained active under reducing conditions when separated into 60 kDa subunits. In L. longipalpis and P. perniciosus the activity was detectable under non-reducing conditions only. In P. duboscqi, low enzyme activity was found also in males. Salivary gland hyaluronidases of sand flies share characteristics with endo-N-acetyl-hexosaminidases of mammalian sperm cells and corresponding venom enzymes of Hymenoptera. Hypothetically, they facilitate blood meal acquisition but also may modulate immune reactions of the host and promote pathogen transmission.
Insect Biochem Mol Biol 2002 Dec
PMID:Salivary gland hyaluronidase in various species of phlebotomine sand flies (Diptera: psychodidae). 1242 21

The present study attempts to establish the isoforms of hyaluronidase enzyme and their possible role in the spreading of toxins during envenomation. Screening of venoms of 15 snakes belonging to three different families revealed varied hyaluronidase activity in ELISA-like assay, but with relatively similar pH and temperature optima. The zymograms of individual venoms showed varied activity banding patterns and indicated the presence of at least two molecular forms of the enzyme. During envenomation, activity of hyaluronidase is considered crucial for the spreading of toxins and is presumed to distort the integrity of extracellular matrix through the degradation of hyaluronic acid in it. This property has been addressed through localization of hyaluronic acid in human skin and muscle tissue sections using the probe, biotinylated hyaluronic acid binding protein. Faint and discontinuous staining pattern of hyaluronidase treated tissue sections over intense staining of untreated tissue sections confirm the selective degradation of hyaluronic acid in extracellular matrix and thus provide an evidence for the spreading property of the enzyme.
Mol Cell Biochem 2002 Nov
PMID:Snake venom hyaluronidase: an evidence for isoforms and extracellular matrix degradation. 1248 77

Glutathione (GSH) content in mature porcine oocytes is correlated with subsequent fertilization and developmental success. Adenosine triphosphate (ATP) is an important energy source for maintaining cellular activities and protein synthesis. The objective of this study was to compare GSH and ATP concentrations of in vivo and in vitro matured porcine oocytes. Ovulated, in vivo matured oocytes were frozen at -80 degrees C in groups of 10-20 (GSH) or 5-10 (ATP). In vitro oocytes were matured in either tissue culture medium-199 (TCM199) supplemented with polyvinyl alcohol (PVA) or hyaluronic acid (MAP5), or North Carolina State University-23 (NCSU23) supplemented with porcine follicular fluid (pFF) and frozen as described, or fertilized and cultured. GSH content was determined by the dithionitrobenzoic acid-glutathione disulfide (DTNB-GSSG) reductase recycling assay. ATP content was determined by using the Bioluminescent Somatic Cell Assay Kit. Oocytes matured in vitro in defined TCM199 with PVA or hyaluronic acid, or NCSU23 with pFF had significantly lower concentrations (P < 0.05) of GSH (n = 207, 9.82 +/- 0.71 pmol/oocyte; n = 104, 9.73 +/- 0.81 pmol/oocyte; n = 108, 7.89 +/- 0.66 pmol/oocyte, respectively) compared to in vivo matured oocytes (n = 217, 36.26 +/- 11.00 pmol/oocyte). Concentrations of ATP were not different between treatments (in vivo, n = 70, 0.97 +/- 0.07 pmol/oocyte; TCM-PVA, n = 117, 0.81 +/- 0.13 pmol/oocyte; TCM-MAP, n = 107, 1.02 +/- 0.18 pmol/oocyte; NCSU-pFF, n = 134, 0.71 +/- 0.08 pmol/oocyte). Intracellular ATP content does not appear to be related to developmental potential in porcine oocytes. Low intracellular GSH may be responsible, in part, for lower developmental competence observed in in vitro matured porcine oocytes.
Mol Reprod Dev 2003 Apr
PMID:Glutathione and adenosine triphosphate content of in vivo and in vitro matured porcine oocytes. 1258 61

Oocyte maturation is accompanied by differentiation of surrounding cumulus cells. These cells produce hyaluronic acid (HA) and its storage in intercellular spaces results in expansion of the cells. The cumulus cells also accumulate cyclooxygenase-2 (cox-2) during maturation. Both expansion and cox-2 storage are regulated by FSH and EGF. The aim of this study was to determine whether oocyte meiotic resumption is involved in the regulation of cumulus differentiation or not. We investigated the effects of roscovitine, a reversible inhibitor of meiosis resumption of cattle oocytes on EGF induced expansion and cox-2 expression at the transcript and protein levels respectively (RT-PCR and Western blot), in cumulus oocyte complexes (COCs) and cumulus complexes alone (CCs). EGF induced expansion and cox-2 expression in both COCs and CCs. These effects were prevented by roscovitine, whether in the presence or in the absence of oocyte. However, the oocyte was essential for the reversibility of inhibition by roscovitine. In conclusion, our results indicate that i) oocyte secreted-factors are not essential for cumulus expansion, and ii) roscovitine mediated inhibition of meiotic resumption also respects the functionality of the surrounding somatic cells.
Mol Reprod Dev 2003 May
PMID:Effect of roscovitine, a cdk1 inhibitor, and of the presence of oocyte on bovine cumulus cell expansion and cyclooxygenase-2 expression. 1265 40

In airways, the cell surface molecule CD44 is upregulated on bronchial epithelial cells in areas of damage. We have shown that a blocking standard CD44 (CD44s) antibody caused a 77% (+/- 19%) inhibition of cell migration at 3 h after mechanical damage and decreased epithelial cell repair of cells grown on cell culture filter inserts. With the use of primary human bronchial epithelial cells and the bronchial epithelial cell line 16HBE 14o-, a CD44s antibody inhibited >95% (P < 0.01) of cell binding to hyaluronic acid (HA). The cytokines TNF-alpha, IFN-gamma, IL-1 beta, and IL-4 stimulated a 2- to 3.5-fold increase in CD44-dependent cell binding to HA. IFN-gamma treatment did not increase CD44 expression as assessed by flow cytometry, although phorbol myristate acetate treatment did. This indicates that IFN-gamma-induced cell binding to HA did not require increased CD44 expression. These data indicate that CD44 is important for bronchial epithelial cell binding to HA and that cytokines known to be expressed in inflammation can increase HA binding independently of the level of CD44 expression.
Am J Physiol Lung Cell Mol Physiol 2003 Dec
PMID:Inflammatory cytokines can enhance CD44-mediated airway epithelial cell adhesion independently of CD44 expression. 1290 89

The relationship between human sperm maturity and apoptosis is of interest because of the persistence of immature sperm in ejaculates in spite of various apoptotic processes during spermatogenesis. We assessed sperm maturity by HspA2 chaperone levels, and plasma membrane maturity by sperm binding to immobilized hyaluronic acid (HA). We also utilized objective morphometry. Sperm were stained with three antibody combinations: active caspase-3/creatine kinase (CK, a marker of cytoplasmic retention), caspase-3/the antiapoptotic Bcl-(XL), and CK/Bcl-(XL). In semen, 13% of sperm stained with CK, caspase-3 or Bcl-(XL), and 28% had stained with two markers. In the mature HA-bound sperm fraction, <4% were single- or double-stained. Regarding sperm regions, CK staining, whether alone or as double staining, occurred in the head and midpiece (15-20%), whereas caspase-3 and Bcl-(XL) were primarily (>80% of sperm) in the midpiece. Morphometrical attributes of clear, single- and double-stained sperm, in line with their more pronounced maturation arrest, showed an incremental increase in head size (due to cytoplasmic retention) and shorter tail length. We hypothesize that during faulty sperm development, three alternatives may occur: (i) elimination of aberrant germ cells by apoptosis; (ii) in surviving immature cells, caspase-3 is activated, and in response the antiapoptotic Bcl-(XL), and perhaps HspA2, provide protection; (iii) in a third type of immature sperm, in addition to the CK, caspase-3 and Bcl-(XL) expression, there are related manifestations of increased head size and shorter tail length. Thus, immature sperm may vary in the type of developmental arrest and in protection mechanisms for apoptosis. These variations are likely to explain the persistence of immature sperm in the ejaculate.
Mol Hum Reprod 2004 May
PMID:Cellular maturity and apoptosis in human sperm: creatine kinase, caspase-3 and Bcl-XL levels in mature and diminished maturity sperm. 1504 2

Both hyaluronic acid (HA) and cyclooxygenase-2 (COX-2) inhibitors are used in clinical practice in the treatment of osteoarthritis. There have been no reports regarding cross-talk between HA and COX-2 inhibitors in articular human chondrocytes. The purpose of this study was to investigate whether HA, COX-2 inhibitors or a combination of COX-2 inhibitors and HA have different effects in human articular between lower and highly degenerated chondrocytes. Isolated lower and highly degenerated chondrocytes were divided into 5 groups: ethanol (used as a control for the solvents), HA, COX-2 inhibitors, COX-2 inhibitors plus HA, or no additive. After incubating for 48 h, mitochondrial membrane potential analysis and western blotting of p38 and p44/42 mitogen-activated protein kinase (MAPK) were performed. Glycosaminoglycan, nitric oxide (NO) production and prostaglandin E2 (PGE2) concentrations were assessed. A combination of COX-2 inhibitors and HA resulted in dendritic, proliferating chondrocytes with strong red fluorescence enriched in the mitochondrial membrane, and indicated reduction of apoptosis in chondrocytes. COX-2 inhibitors alone, and a combination of COX-2 inhibitor and HA inhibited the activation of p38 in highly degenerated chondrocytes. A combination of COX-2 inhibitors and HA decreased NO production in highly degenerated chondrocytes. COX-2 inhibitors decreased PGE2 production, however, HA alone had no effect on PGE2 production. The present study demonstrated that COX-2 inhibitors and HA interacted synergistically the MAPK pathway and inhibition of NO production in highly degenerated chondrocytes. Administration of COX-2 inhibitors plus HA could be used as a new alternative way of treating osteoarthritis.
Int J Mol Med 2004 Aug
PMID:Cross talk between COX-2 inhibitor and hyaluronic acid in osteoarthritic chondrocytes. 1525 55

Laboratory tests for the noninvasive diagnosis of liver fibrosis were studied extensively in the past. However, no test is yet accepted to replace liver biopsy as the gold standard. The establishment of widely accepted semiquantitative histologic scoring systems for the grading and staging of chronic liver disease (e.g., Ishak, Metavir and Scheuer) was paralleled by a significant upturn of research in circulating markers of liver fibrosis. We are now experiencing the renaissance of standard clinical chemistry markers, which are assembled to multiparameter scores (e.g., aspartate aminotransferase-to-platelet ratio index, FibroTest, Forns' index). These scores still require comprehensive evaluation in comparison with histology. Better understanding of the pathophysiology of liver fibrosis provided new options regarding circulating markers of hepatic matrix metabolism (e.g., hyaluronic acid, laminin, matrix metalloproteinase-2, aminoterminal propeptide of procollagen type III and tissue inhibitors of metalloproteinases-1). Several promising studies have been published to date. Thus, a redefinition of the role of liver biopsy is expected in the foreseeable future.
Expert Rev Mol Diagn 2004 Sep
PMID:Noninvasive diagnosis of fibrosis in chronic liver disease. 1534 64

Transcription of the majority of the members of the Plasmodium falciparum var multigene family were analysed in two isolates by a quantitative approach. Both of these isolates had been repeatedly selected for adhesion to chondroitin sulphate A (CSA) and one had also been selected for adhesion to hyaluronic acid (HA). These adhesion phenotypes are expressed by many parasites isolated from placentae and are associated with malaria disease in pregnancy. Increased transcription of the var gene var2csa, or its homologue IT4 var4, was associated with the CSA and HA adhesion phenotypes in all parasites suggesting that it was the dominant, if not the only, var gene that encoded adhesion to CSA in these allogeneic isolates. Some var genes were consistently transcribed at higher levels than others regardless of expressed adhesion phenotypes suggesting a transcriptional hierarchy. Unspliced or partial transcripts were detected for most var genes tested. These atypical var gene transcripts may have implications for the regulation of var gene transcription.
Mol Microbiol 2005 May
PMID:Broad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype. 1581 31

Using the hyaluronic acid (HA) binding region of the receptor for hyaluronan-mediated motility (RHAMM) as a model, a molecular perspective for peptide mimicry of the natural ligand was established by comparing the interaction sites of HA and unnatural peptide-ligands to RHAMM. This was accomplished by obtaining a series of octapeptide-ligands through screening experiments that bound to the HA binding domains of RHAMM (amino acids 517-576) and could be displaced by HA. These molecules were computationally docked onto a three-dimensional NMR based model of RHAMM. The NMR model showed that RHAMM(517-576) was a set of three helices, two of which contained the HA binding domains (HABDs) flanking a central groove. The structure was stabilized by hydrophobic interactions from four pairs of Val and Ile side chains extending into the groove. The presence of solvent exposed, positively charged side chains spaced 11 A apart matched the spacing of negative charges on HA. Docking experiments using flexible natural and artificial ligands demonstrated that HA and peptide-mimetics preferentially bound to the second helix that contains HABD-2. Three salt bridges between HA carboxylates and Lys548, Lys553 and Lys560 and two hydrophobic interactions involving Val538 and Val559 were predicted to stabilize the RHAMM-HA complex. The high affinity peptides and HA utilized the same charged residues, with additional contacts to other basic residues. However, hydrophobic contacts do not contribute to affinity for peptide ligand-RHAMM complexes. These results offer insight into how selectivity is achieved in the binding of HA to RHAMM, and how peptide competitors may compete for binding with HA on a single hyaladherin.
J Comput Aided Mol Des 2004 Oct
PMID:Interactions of peptide mimics of hyaluronic acid with the receptor for hyaluronan mediated motility (RHAMM). 1584 92


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