Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.2.1.36 (
hyaluronidase
)
4,606
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Actinomycin D (ActD) enhances the potency of tumor necrosis factor-alpha (TNF-alpha) in killing cancer cells. However, it is determined in this study that murine L929 fibrosarcoma cells, when pretreated with bovine testicular
hyaluronidase
for 12-24 h, became resistant to the cytotoxic effect of TNF-alpha in the presence of DNA intercalators, such as ActD, doxorubicin, and daunorubicin. Monoclonal anti-Fas antibody-mediated apoptosis in the presence of ActD was also blocked in
hyaluronidase
-pretreated L929 cells. Hyaluronidase failed to up- or downregulate the expression of apoptosis regulatory proteins, including Bcl-2, Bcl-xL, ICH-1, and TIAR, suggesting that these proteins were not involved in the
hyaluronidase
-induced resistance to TNF/ActD. A semisynthetic polysulfated hyaluronic acid (HA) inhibited the increased TNF/ActD resistance, whereas unmodified HA, dextran sulfate, and naturally polysulfated glycosaminoglycans had no effect. Evidence is provided here that the induced resistance is related to serum fetuin and a novel intracellular 35-kDa TNF-binding protein (intra
TBP
). Under serum-free conditions, L929 became refractory to TNF/ActD cytotoxicity and
hyaluronidase
reversed the resistance. Exogenous fetuin increased L929 cell spreading and proliferation, and restored
hyaluronidase
-induction of TNF/ActD resistance in these serum-starved cells. Hyaluronidase failed to reduce the expression of TNF-receptors and their binding of TNF-alpha. However, binding and Western-blotting analyses revealed that
hyaluronidase
downregulated the intra-
TBP
. Overall, these observations suggest that serum fetuin and intraTBP are involved in the
hyaluronidase
induction of TNF/ ActD resistance.
...
PMID:Hyaluronidase induces murine L929 fibrosarcoma cells resistant to tumor necrosis factor and Fas cytotoxicity in the presence of actinomycin D. 910 95
