Disease relevance of Acetyl ceramide

• Here, we report that glioma cells are also susceptible to the cytotoxic effects of exogenous C2-ceramide [1].
• Addition of exogenous C2-ceramide induced cell death and activated caspase-3 as markedly as the hypoxia treatment [2].
• Furthermore, only C2-ceramide stimulated an induction of cell cycle arrest that was associated with stable expression of p21CIP1 and retinoblastoma nuclear phosphoprotein dephosphorylation [3].
• Importantly, C2-ceramide-induced suppression of calpain phosphorylation results in decreased secretion of mu- and m-calpains from lung cancer cells into culture medium, which may have potential clinic relevance in controlling metastasis of lung cancer [4].
• Prevalence of necrosis in C2-ceramide-induced cytotoxicity in NB16 neuroblastoma cells [5].

Psychiatry related information on Acetyl ceramide

• IL-6 (1-10 ng/ml) potentiated C2-ceramide effects in cultured hepatocytes while decreasing by itself MAT I/III levels with a similar time-response curve in both cell types [6].

High impact information on Acetyl ceramide

• The effects of C2-ceramide on DNA fragmentation were prevented by the protein kinase C activator phorbol 12-myristate 13-acetate, which suggests the existence of two opposing intracellular pathways in the regulation of apoptosis [7].
• Other stimuli such as C2-ceramide were capable of inducing rapid apoptosis in OLs [8].
• We found that submicromolar concentrations of C2-ceramide induced IL-6 gene expression and protein production as effectively as IL-1 beta [9].
• Finally, all CD95-sensitive cell lines tested could be induced to undergo apoptosis after exposure to cell-permeant C2-ceramide [10].
• This effect was mimicked by sphingomyelinase, but not by phospholipase A2 or phospholipase C. C2-ceramide induced IL-8 gene transcription mainly through activation of NF-kappaB because mutation of the NF-kappaB-binding site completely abrogated the induction of luciferase activity [11].

Chemical compound and disease context of Acetyl ceramide

• Exposure of LLC-PK1 cells to synthetic ceramide, C2- and C6-ceramide, but not C2-dihydroceramide, the structural analog of C2-ceramide, resulted in DNA strand breaks, DNA fragmentation and cell death in a dose- and time-dependent manner similar to the effect of chemical hypoxia [12].
• Inhibition of skin carcinomas but not papillomas by sphingosine, N-methylsphingosine, and N-acetylsphingosine [13].
• METHODS.: We used L1 transfectants and ovarian carcinoma cell lines and induced apoptosis by different stimuli such as C2-ceramide, staurosporine, cisplatin or hypoxia [14].
• Ionomycin was found to increase the release of HSV-1, whereas no significant increase was observed by the treatment with TNF-alpha, anti-Fas antibody, C2-ceramide, sphingosine, H-7, tyrphostin and camptothecin [15].

Biological context of Acetyl ceramide

• Finally, Z-VAD-FMK and the PP2A inhibitor okadaic acid both prevented the impairment of Tau phosphorylation induced by C2-ceramide [16].
• These actions of C2-ceramide on cell motility and neurite outgrowth were accompanied by a disorganization of the actin filament network, depolarization of tubulin, and alteration of the microtubule-associated protein Tau [16].
• After stimulation with cell-permeable C2-ceramide or mitochondrial permeability transition (PT) inducers, not only apoptosis-sensitive cell lines (HL-60, Jurkat, and Daudi cells), but also Raji cells showed reduction of the mitochondrial transmembrane potential (triangle uppsim), activation of caspase-3, and loss of clonogenic potential [17].
• Apoptotic DNA fragmentation after exposure to TNF-alpha and C2-ceramide was also associated with down-regulation of Bcl-2 mRNA in HL-60 and U-937 cells, while Bcl-X mRNA production was unaffected [18].
• The addition of exogenous, cell-permeable C2-ceramide to the Hs 27 human diploid fibroblast cell line resulted in a dose-dependent induction of the p21WAF1/CIP1/Sdi1 kinase inhibitor with reduction of cyclin-D1 associated kinase activity [19].

Anatomical context of Acetyl ceramide

• Expression of DINE in COS cells partially inhibited C2-ceramide-induced apoptosis, probably because of the activation of antioxidant enzymes such as Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, and glutathione peroxidase through the proteolytic activity of DINE [20].
• (ii) Wild-type virus protected subconfluent SK-N-SH but not HeLa cells against induction of apoptosis by anti-Fas antibody, TNFalpha, C2-ceramide, and thermal shock [21].
• Electrophysiological experiments on preoptic area/anterior hypothalamic neurons show that C2-ceramide, but not dihydroceramide, mimics the rapid hyperpolarizing effects of IL-1beta on the activity of warm-sensitive hypothalamic neurons [22].
• Insulin-like growth factor-1 (IGF-1) inhibited N-acetylsphingosine (C2-ceramide)-induced HL-60 cell apoptosis via relieving oxidative damage [23].
• Furthermore, exogenous C2-ceramide was cytotoxic to bovine brain endothelial cells and induced activation of C-jun N-terminal kinase (JNK), a MAP kinase that can be activated in stress-induced apoptosis pathways [24].

Associations of Acetyl ceramide with other chemical compounds

• However C2-ceramide, a cell permeant synthetic analog of ceramide, could efficiently induce apoptosis in T-LPL and T-PBL when added exogenously [25].
• We investigated the ability of the virus to protect cells in continuous cultivation from apoptosis induced by the virus itself, and by other known inducers such as exposure to the tumor necrosis factor alpha (TNFalpha), antibody to Fas, C2-ceramide, osmotic shock (sorbitol), and thermal shock [21].
• We found that induction of apoptosis in Mphi by oxLDL, C2-ceramide, tumor necrosis factor alpha (TNF-alpha), and hydrogen peroxide (H2O2) was associated with enhanced expression of manganese superoxide dismutase (MnSOD) and p53 [26].
• Okadaic acid decreased the activation of phospholipase D by sphingosine 1-phosphate and did not reverse the inhibitory effect of C2-ceramide on this activation [27].
• However, C2-ceramide had no effect on Ag-induced protein tyrosine phosphorylation, including mitogen-activated protein (MAP) kinases [28].

Gene context of Acetyl ceramide

• Furthermore, TNF alpha, sphingomyelinase, and C2-ceramide induce c-jun, a gene that is stimulated by the ATF-2 and c-Jun transcription factors [29].
• While PMA activated extracellular signal-regulated kinase (ERK), a downstream kinase of Raf-MEK signaling, C2-ceramide activated c-Jun NH2-terminal kinase (JNK), an anchor kinase of stress-induced signaling [3].
• ERK activation was enhanced by C2-ceramide plus PMA stimulation, whereas the activation of JNK was aborted [3].
• Further, JNK/SAPK activity is stimulated 2.7- and 2.8-fold, respectively, in cells exposed to C2-ceramide (5 microM) or TNF alpha (10 ng/ml) [29].
• In contrast, the related mitogen-activated protein kinases ERK1 and ERK2 are weakly stimulated following TNF alpha treatment (1.5-fold) and are inhibited by C2-ceramide treatment [29].

Analytical, diagnostic and therapeutic context of Acetyl ceramide

• Both HS and N-acetylsphingosine (C(2)-ceramide) increased the expression of c-jun/c-fos mRNAs with the peak 2 h after treatment [30].
• A short-chain ceramide analog, C2-ceramide, completely precluded insulin-stimulated glucose uptake and insulin-induced GLUT4 translocation to plasma membrane, as determined by Western blot or immunofluorescent localization of GLUT4 [31].
• In Jurkat T cells, Fas ligation or addition of exogenous C2-ceramide induced activations of caspase-3/CPP32 and caspase-7/Mch3 followed by PARP cleavage, effects that can be blocked either by SPP or TPA [32].
• Northern blot analyses revealed that C2-ceramide and sphingomyelinase increased interleukin-1 beta-induced E-selectin gene transcription levels [33].
• In separate experiments, brains of sham-operated control and HI only animals and animals subjected to HI plus C2-ceramide or DMSO infusion were sampled 6 hours, 24 hours, and 5 days after treatments and analyzed for Bcl-2, Bcl-xl, and Bax expression (Western blotting), and apoptosis (TUNEL assay) [34].

References