EC Number   |
General Information |
Reference |
|---|
    1.14.19.17 | malfunction |
DEGS1 ablation induces fat body cell hypertrophy, increased fat body lipid droplet size, and increased abdominal adiposity. In flies, genetic ablation of ifc gene (orthologue for degs1) causes an obese phenotype (larger fat bodies) independent of the caloric intake |
744398 |
| 1.14.19.17 | malfunction |
DEGS1 inhibition enhances insulin sensitivity, DEGS1 ablation induces autophagy and blocks cellular proliferation, and provides protection from chemotherapeutic agents through the activation of prosurvival pathways. Homozygous DEGS1 knockout mouse exhibits a severe phenotype characterised by low survival rate and multiple abnormalities. The heterozygous mice are viable with normal birth Mendelian rates, superficial biochemical phenotypical analysis reveals that mutant degs1 hets mice show higher DhCer/Cer ratios in multiple organs. This is associated with enhanced insulin sensitivity, normal glucose tolerance and resistance to dexamethasone induced insulin resistance. Embryonic fibroblasts from DEGS1knockout mice show enhanced AKT signalling, likely due to the absence of ceramides and not a result of the direct effect of dihydroceramide accumulation. DEGS1 heterozygotes gain more weight over time in comparison to wild-type mice |
744398 |
| 1.14.19.17 | malfunction |
DES1 inhibition by specific siRNA causing DES1 activity decrease can ameliorate the increase in ceramide, enhance dihydroceramide elevation, and inhibit the palmitic acid-induced increases in caspase 9 activity and caspase 3 activity, palmitic acid-mediated apoptosis and cell growth inhibition are also attenuated by DES1 downregulation |
744061 |
| 1.14.19.17 | malfunction |
Des1 inhibition is primarily responsible for the antiproliferative effects of SKI-II and its analogues. The structure-activity relationship of Des1 inhibition correlates to that required for inhibition of PC-3 cell growth, indicating that Des1 inhibition is a key driver of the anticancer effects of SKI-II and it analogues, which is also supported by lipidomic studies in PC-3 cells |
745527 |
| 1.14.19.17 | malfunction |
DESG1 inhibition block the cell growth, cell migration, cytoskeleton modification, response to insulin, impair of endomembrane trafficking. Fenretinide can exert part of its insulin sensitising effects in liver and muscle by inhibiting DEGS1 and hence decreasing the synthesis of ceramides with the concomitant increase in diydroceramide levels |
744398 |
| 1.14.19.17 | malfunction |
dihydroceramide desaturase 1 inhibitors activate autophagy via both dihydroceramide-dependent and independent pathways and the balance between the two pathways influences the final cell fate. Enzyme inhibitors celecoxib, resveratrol, phenoxodiol, and gamma-tocotrienol, but not gamma-tocopherol at 0.05 mM, promote an increase in dihydroceramide, dihydrosphingomyelins, and lactosyldihydroceramides in U-87MG and T-98G cell lines. Similar results are found with the active site-directed Des1 inhibitor XM462 |
744418 |
| 1.14.19.17 | malfunction |
gamma-tocotrienol inhibits cellular dihydroceramide desaturase (DEGS) activity without affecting its protein expression or de novo synthesis of sphingolipids. Unlike the effect on dihydroceramides, gamma-tocotrienol decreases ceramides (Cers) after 8-h treatment but increases C18:0-Cer and C16:0-Cer after 16 and 24 h, respectively. The increase of ceramides coincides with gamma-tocotrienol-induced apoptosis and autophagy. Since gamma-tocotrienol inhibits DEGS and decreases de novo ceramide synthesis, elevation of ceramides during prolonged gamma-tocotrienol treatment is likely caused by sphingomeylinase-mediated hydrolysis of sphingomyelin. gamma-Tocotrienol treatment led to a time- and dose-dependent decrease in viability of colon, pancreatic and breast cancer cells, overview |
745595 |
| 1.14.19.17 | malfunction |
homozygous DES1-null mice are viable, they fail to thrive and have numerous health abnormalities, dying within the first 8-weeks of age. In contrast, the heterozygous mice are viable with normal Mendelian birth rates. Lipid analysis reveal that DES1 heterozygous mice show higher dhCer/Cer ratios in multiple organs. Importantly, these mice are protected from glucocorticoid-, saturated fat- and obesity-induced insulin resistance, as well as from diet-induced hypertension. Cells from DES1 null mice are resistant to apoptosis, and, although they exhibit a remarkably strong activation of protein kinase B, they show high levels of autophagy. The latter results from activation of AMP-activated protein kinase. Therefore, ablation of DES1 simultaneously stimulates anabolic and catabolic signaling through activation of protein kinase B and AMP-activated protein kinase pathways, respectively. Activation of pro-survival and anabolic signaling intermediates provided protection from apoptosis caused by etoposide. Heterozygous deletion of DES1 prevented vascular dysfunction and hypertension in mice after high-fat feeding |
744686 |
| 1.14.19.17 | malfunction |
increased DEGS1 activation through myristoylation induces apoptosis mediated by the increase of ceramides |
744398 |
| 1.14.19.17 | malfunction |
inhibitors SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 in LNCaP-AI prostate cancer cells. Inhibitors SKi, ABC294640, or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 fails to increase p53 and p21 expression, but the former reduces DNA synthesis in LNCaP-AI prostate cancer cells. N-acetylcysteine (reactive oxygen species scavenger) blocks the SK inhibitor-induced increase in p21 and p53 expression but has no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increases p53 expression while a combination of Des1/SK1 siRNA increases the expression of p21. Modulation of both de novo and sphingolipid rheostat pathways in order to induce growth arrest can be achived by targeting androgen-independent prostate cancer cells with compounds that affect the enzymes Des1 and SK1. N-acetyl cysteine has no effect on the ABC294640-induced proteasomal degradation of Des1, suggesting that the oxidative stress response is down stream of Des1 |
745943 |
