Ceramidase and ceramide synthesis in human kidney and cerebellum

Sugita, Mutsumi; Willians, M; Dulaney, John T.; Moser, Hugo W.

doi:10.1016/0005-2760(75)90176-9

Cited by 181 publications

(105 citation statements)

References 16 publications

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“…Most likely due to defective intracellular ceramide degradation, C2-ceramide was signi®cantly more toxic in Farber cells than in normal counterparts ( Figure 4b). As expected and demonstrated in Figure 4c, Farber disease cells were also more sensitive to low concentrations (5 mM) of the ceramide analog Noleoylethanolamine (NOE) that is a potent inhibitor of ceramidase activity (Sugita et al, 1975). High concentrations (50 mM) of NOE, which presumably inhibit additional ceramidases and enzymatic reactions such as ceramide glucosylation (Spinedi et al, 1999), equally induced apoptosis in Farber and normal primary blood lymphocytes.…”

Section: Farber Lymphoid Cells Are More Sensitive To Cd95-and Ceramidsupporting

confidence: 71%

The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells

et al. 2001

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The activation of sphingomyelinases leading to the generation of ceramide has been implicated in various apoptotic pathways. However, the role of ceramide as an essential death mediator remains highly controversial. In the present study, we investigated the functional relevance of ceramide in a genetic model by using primary cells from a Farber disease patient. These cells accumulate ceramide as the result of an inherited deficiency of acidic ceramidase. We demonstrate that Farber disease lymphocytes and fibroblasts underwent apoptosis induced by various stress stimuli, including staurosporine, anticancer drugs and gamma -irradiation, equally as normal control cells. In addition, caspase activation by these proapoptotic agents occurred rather similarly in Farber disease and control fibroblasts. Interestingly, Farber disease lymphoid cells underwent apoptosis induced by the CD95 death receptor more rapidly than control cells. Our data therefore suggest that ceramide does not play an essential role as a second messenger in stress-induced apoptosis. However, in accordance with a role in lipid-rich microdomains, ceramide by altering membrane composition may function as an amplifier in CD95-mediated apoptosis

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Section: Farber Lymphoid Cells Are More Sensitive To Cd95-and Ceramidsupporting

confidence: 71%

The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells

et al. 2001

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“…To establish the relationship between ASMase/ACDase activation and hepatic ceramide accumulation, we tested the effect of inhibition of both enzymes in ceramide homeostasis during I/R. Imipramine, which prevents ASMase activation, 16,33 and Noleoylethanolamine (NOE), a potent ACDase inhibitor, 21,34 were administered 30 minutes before surgery. Imipramine, which prevented the I/R-induced ASMase activation, decreased the peak of ceramide levels generated 30 minutes after reperfusion (Fig.…”

Section: Resultsmentioning

confidence: 99%

Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury

et al. 2006

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The molecular mechanisms of hepatic ischemia/reperfusion (I/R) damage are incompletely understood. We investigated the role of ceramide in a murine model of warm hepatic I/R injury. This sphingolipid induces cell death and participates in tumor necrosis factor (TNF) signaling. Hepatic ceramide levels transiently increased after the reperfusion phase of the ischemic liver in mice, because of an early activation of acidic sphingomyelinase (ASMase) followed by acid ceramidase stimulation. In vivo administration of an ASMase inhibitor, imipramine, or ASMase knockdown by siRNA decreased ceramide generation during I/R, and attenuated serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation. ASMase-induced ceramide generation activated JNK resulting in Bim L phosphorylation and translocation to mitochondria, as the inhibition of ASMase by imipramine prevented these events. In contrast, blockade of ceramide catabolism by N-oleyolethanolamine (NOE), a ceramidase inhibitor, enhanced ceramide levels and potentiated I/R injury compared with vehicle-treated mice. Pentoxifylline treatment prevented TNF upregulation and ASMase activation. Furthermore, 9 of 11 mice treated with imipramine survived 7 days after total liver ischemia, compared with 4 of 12 vehicle-treated mice, whereas 8 of 8 NOE-treated mice died within 2 days of total liver ischemia. In conclusion, ceramide generated from ASMase plays a key role in I/R-induced liver damage, and its modulation may be of therapeutic relevance.

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“…To examine if acid CDase downregulation regulated ceramide homeostasis after DNR treatment, ceramide levels were measured in AC siRNA-transfected HepG2 cells. Ceramide basal levels (1.870.1 mg/mg protein), moderately increased by DNR treatment, were significantly Acid CDase inhibition by NOE enhances the ceramide to S1P balance and sensitizes hepatoma cells to DNR To evaluate whether N-oleoylethanolamine (NOE), a potent CDase inhibitor (Sugita et al, 1975;Strelow et al, 2000;Monick et al, 2004) recapitulates the effects observed upon acid CDase downregulation, we determined ceramide levels in HepG2 cells in response to DNR with or without acid CDase inhibition by NOE.…”

Section: Dnr Activates Acid Cdase In Hepatoma Cellsmentioning

confidence: 99%

Pharmacological inhibition or small interfering RNA targeting acid ceramidase sensitizes hepatoma cells to chemotherapy and reduces tumor growth in vivo

et al. 2006

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Ceramidase and ceramide synthesis in human kidney and cerebellum

Cited by 181 publications

References 16 publications

The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells

The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells

Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury

Pharmacological inhibition or small interfering RNA targeting acid ceramidase sensitizes hepatoma cells to chemotherapy and reduces tumor growth in vivo

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