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)

Previously we have shown that TGF-beta1 protects murine L929 fibroblasts from TNF/ActD-mediated cell death by inducing the expression of an extracellular matrix TNF-resistance triggering (TRT) protein. TRT promotes TNF-resistance via activation of tyrosine and serine/threonine kinases in L929 cells. To examine the presence of TRT activity in serum (designated STRT), human sera were diluted, treated with or without PMSF and subjected to sequential ammonium sulfate precipitation (ASP). Aliquots of the ASP protein fractions were coated onto 96-well plates, followed by thorough washing. When L929 cells were seeded and cultured on the wells coated with STRT proteins, these cells resisted killing by TNF, TNF/ActD, doxorubicin and serum deprivation, but not by anti-Fas/ActD, staurosporine and ActD. STRT activity was found at the 15% ASP fraction of untreated sera, but shifted to the 20% ASP fraction of PMSF-treated sera. Two likely STRT proteins of approximately 226 and 265 kDa were found in these fractions, compared to the corresponding nonfunctional ASP fractions. Functionally, STRT was inactivated by trypsin, but not by 5 M salt, various serine and/or cysteine protease inhibitors, and antibodies against fibronectin, vitronectin, C1q, histidine-rich glycoprotein, CD44, chondroitin sulfate and hyaluronic acid. STRT failed to alter the expression of proteins involved in apoptosis such as RIP, ICH-1L, BCL-X, TIAR and IkappaBalpha, and could not induce IkappaBalpha degradation. The induced TNF-resistance could be reversed by treatment of STRT-stimulated cells with testicular hyaluronidase, as well as with tyrosine kinase inhibitors tyrophostin, lavendustin A and AG-490 (a selective inhibitor of JAK2 kinase). However, the STRT function could not be blocked by the MEK kinase inhibitor PD98059 and the NF-kappaB inhibitors curcumin and a synthetic inhibitor peptide for NF-kappaB translocation. Together, our data suggest that tyrosine kinase activation is involved in the STRT-mediated resistance to TNF and TNF/ActD in L929 cells.
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PMID:Characterization of serum adhesive proteins that block tumor necrosis factor-mediated cell death. 1646 90

Cystitis cystica et glandularis (CCEG) is a chronic cystitis that causes extreme agony in affected patients. However, there are lack of effective conservative treatments. In this study, it is evident that intravesicular sodium hyaluronate (SH) therapy significantly improved the clinical symptoms of CCEG patients and ameliorated the bladder mucosal inflammation and cell proliferation characteristics of the disease. Immunohistochemical staining showed that the staining intensities of hyaluronidase (HYAL 1/2), CD44, IL-6 and phosphorylated signal transducer and activator of transcription 3 (p-Stat3) in bladder mucosal tissue were significantly increased in CCEG patients compared with control patients and that intravesicular SH treatment suppressed these protein expression. We established a CCEG rat model by treating rats with E. coli intravesicularly, and we found that HYAL 1/2 and CD44 expression levels were significantly increased in the E. coli group compared with the NC group. Activation of the IL-6/JAK2/Stat3 pathway and the expression levels of the downstream pro-apoptotic proteins Mcl-1 and Bcl-xL were also significantly increased in the E. coli group compared with the NC group. The above changes were significantly mitigated by intravesicular SH treatment. Therefore, SH may serve as an effective therapy for CCEG by inhibiting bladder mucosal inflammation and proliferation.
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PMID:Intravesicular administration of sodium hyaluronate ameliorates the inflammation and cell proliferation of cystitis cystica et glandularis involving interleukin-6/JAK2/Stat3 signaling pathway. 2916 39