Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ceramide lactoside [1-O-(galactosido-4-beta-glucosido)-2-N-acyl-sphingosine] was hydrolysed to ceramide glucoside and galactose by beta-galactosidase of rat brain. The reaction was not reversible, required cholate or taurocholate, had optimum pH5.0 and K(m) 2.2x10(-5)m. It was inhibited by gamma-galactonolactone and galactose as well as by ceramide, sphingosine and fatty acid. Ceramide lactoside could be degraded to ceramide, galactose and glucose by mixtures of rat-brain beta-galactosidase and ox-brain beta-glucosidase.
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PMID:Enzymic hydrolysis of sphingolipids: Hydrolysis of ceramide lactoside by an enzyme from rat brain. 1674 44

Bioactive sphingolipids are potent intracellular signaling molecules having profound effects on cell death, growth, and differentiation. Pharmacologic manipulation of sphingolipid levels could have a significant effect on the induction of apoptosis by anticancer agents, and thus, improve treatment efficacy. We observed that gemcitabine cannot completely kill AsPc1 and Panc1 human pancreatic cancer cells in culture; even at high concentrations of gemcitabine, 30% to 40% of the cells remain viable. By adding sphingomyelin to the culture medium, gemcitabine-induced cell death increased synergistically to >90%. Panc1 cells that survived high concentrations of gemcitabine had an increase in beta-galactosidase activity, a marker of senescence. The inclusion of sphingomyelin with gemcitabine reduced beta-galactosidase activity, as compared with cells treated with gemcitabine alone. Expression of p21(waf1/cip1) in both cell lines exposed to sphingomyelin, gemcitabine, and gemcitabine + sphingomyelin varied relative to the untreated group. C(8)-ceramide induced both cell death and senescence in a dose-dependent manner. These results indicate that gemcitabine induces senescence in pancreatic cancer cells and that sphingomyelin-enhanced chemosensitivity is achieved through reducing the induction of senescence by redirecting the cell to enter the apoptotic pathway. Ceramide levels seem to be critical to this decision, with cell cycle progression being uninhibited at low ceramide levels, senescence induced at moderate levels, and apoptosis initiated at high levels. Our results provide further evidence that targeting the sphingolipid metabolism is a means of enhancing the efficacy of chemotherapeutic agents.
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PMID:Ceramide regulates gemcitabine-induced senescence and apoptosis in human pancreatic cancer cell lines. 1953 70

Ceramide has been proposed to be a mediator of replicative senescence. Our aim was to determine whether ceramide induces senescence in vascular endothelial cells. Human umbilical vein endothelial cells were cultured to different population doubling levels and ceramide levels were quantitated. The endogenous levels of ceramide increased 2.4-fold with senescence onset. Low passage cells were chronically treated with exogenous C(6)-ceramide. This treatment induced a senescent phenotype as measured by an inhibition of cell proliferation and DNA replication while increasing senescence-associated beta-galactosidase expression. This is the second cell type in which ceramide induces senescence, thus implicating ceramide as a general mediator of cellular senescence.
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PMID:Ceramide induces endothelial cell senescence. 1984 94


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