Ceramide is one of the major sphingosine-based lipid second messengers that is generated in response to various extracellular agents. However, while widespread attention has focused on ceramide as a second messenger involved in the induction of apoptosis, important issues with regard to the mechanisms of ceramide formation and mode of ...

Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. In this study, we show that antisense bax inhibits cytochrome c release, poly(ADP-ribose)polymerase cleavage and cell death induced by ceramide in HL-60 cells. In addition, ceramide induces translocation of Bax to mitochondria. The addition ...

This review describes (from both the animal and human literature) the biological consequences of losses in nervous system docosahexaenoate (DHA). It then concentrates on biological mechanisms that may serve to explain changes in brain and retinal function. Brief consideration is given to actions of DHA as a nonesterified fatty acid ...

Oxysterols, particularly those oxidised at position 7, are toxic to cells in culture and have been shown to induce apoptosis in cell types such as vascular endothelial cells, smooth muscle cells and monocytes. The precise mechanism by which oxysterols induce apoptosis is unknown but may involve the generation of oxidative ...

Ceramide appears to be a potent second messenger implicated in the regulation of diverse cellular processes such as cell growth and differentiation, gene transcription, ligand binding, and cell death. Environmental stress-induced apoptosis is believed to be associated with the sphingomyelin degradation pathway, which generates ceramide as a second messenger in ...

Cr(VI) compounds have been declared as a potent occupational carcinogen by IARC (1990) through epidemiological studies among workers in chrome plating, stainless-steel, and pigment industries. Studies relating to the role of intermediate oxidation states such as Cr(V) and Cr(IV) in Cr(VI)-induced carcinogenicity are gaining importance. In this study, issues relating ...

Granulysin is a cytolytic molecule released by CTL via granule-mediated exocytosis. In a previous study we showed that granulysin induced apoptosis using both caspase- and ceramide-dependent and -independent pathways. In the present study we further characterize the biochemical mechanism for granulysin-induced apoptosis of tumor cells. Granulysin-induced death is significantly inhibited ...

To clarify the chronology of events leading to anti-Fas-induced apoptosis, and the mechanisms of resistance to this death effector, we compared the response kinetics of three tumour cell lines that display varying sensitivity to anti-Fas (based on levels of apoptosis), in terms of ceramide release, mitochondrial function and the caspase-activation ...

Sphingomyelin (SM) is a prominent phospholipid component of cell membranes that has evolved diverse functions in cells beyond its role in membrane structural organization. Cleavage of SM by acid or neutral sphingomyelinase results in the liberation of ceramide, an intracellular messenger that regulates the activities of an array of kinases, ...

Lead (Pb) is an environmental toxicant that can induce structural and functional abnormalities of multiple organ systems, including the central nervous and the immune systems. The aim of this study was to evaluate the effects of extracellular Pb supplementation on the cellular content of the metal and on the proliferation ...

Tumor necrosis factor-alpha and interferon-gamma are pleiotropic cytokines that regulate Schwann cell responses during injury and inflammatory demyelination. We have previously shown that cyclic AMP (cAMP)-elevating agents decrease the demyelination and Wallerian degeneration in experimental allergic neuritis. In this study, we examined the role of cAMP in cytokine-mediated signaling in ...

Ceramide participates in signal transduction of IL-1 and TNF, two cytokines likely involved in cartilage degradation in osteoarthritis. We previously showed that ceramide stimulates proteoglycan degradation, mRNA expression of matrix metalloproteinase (MMP)-1, -3, and -13, and pro-MMP-3 production in rabbit cartilage. Since aggrecan, the main cartilage proteoglycan, can be cleaved ...

Centrosome duplication is a critical step in assembly of the bipolar mitotic spindle, but the molecular mechanisms regulating this process during the cell cycle and during animal development are poorly understood. Here, we report that the zyg-1 gene of Caenorhabditis elegans is an essential regulator of centrosome duplication. ZYG-1 is ...

PURPOSE: Taxol has emerged as a valuable antimitotic chemotherapeutic agent, particularly in advanced breast and ovarian cancers. Although much is known about cytotoxic mechanisms, the effectiveness of Taxol cannot be solely explained by microtubular interaction. This study was undertaken to determine whether ceramide generation plays a role in Taxol-induced apoptosis. ...

Sphingolipids have important roles in membrane and lipoprotein structure and in cell regulation as second messengers for growth factors, differentiation factors, cytokines, and a growing list of agonists. Bioactive sphingolipids are formed both by the turnover of complex sphingolipids and as intermediates of sphingolipid biosynthesis. Usually, the amounts are highly ...

Caspase-dependent apoptosis induced by okadaic acid (OA) in CHP-100 neuroepithelioma cells has previously been shown to associate with a rapid and sustained elevation in intracellular ceramide concentration. We now report that treatment of CHP-100 cells with OA also evoked a rapid elevation in glucosylceramide levels that was maintained at steady ...

The present study was undertaken to investigate the effects of ceramide on progesterone production and apoptosis in rat luteal cells in vitro. Luteal cells were prepared from the ovaries of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) primed female Wistar rats and incubated with cell permeable C2-ceramide. ...

Anthracyclines are, above all, DNA intercalators, which induce genetic damage leading to cell death. However, increasing evidence firmly suggests that the underlying mechanism for anthracycline cytotoxicity is the induction of apoptosis through intracellular-mediated signaling pathways. Whether drug/DNA interaction is necessary for such apoptosis signaling is unknown. We investigated the cellular ...

Ultraviolet light (UV) activates an acid sphingomyelinase (ASMase) pathway, which hydrolyzes sphingomyeline to ceramide. Ceramide has been found to be a second messenger, which activates the c-jun N-terminal kinase (JNK) that is required for apoptotic cell death. However, the role of ceramide in UV-induced JNK activation and apoptosis remains controversial. ...

U1A is a component of the uracil-rich small nuclear ribonucleoprotein. The molecular mechanism of nuclear import of U1A was investigated in vivo and in vitro. When recombinant deletion mutants of U1A are injected into the BHK21 cell cytoplasm, the nuclear localization signal (NLS) of U1A is found in the N-terminal ...

DNA damage has many cellular consequences including, in some cases, apoptosis. Expression of Gadd34 was shown to be increased by ionizing radiation only in cells that undergo rapid apoptosis following this treatment. The effects of various other apoptosis-inducing agents as well as apoptosis-inhibiting genes on regulation of Gadd34 were investigated. ...

Polyamines are aliphatic cations with multiple functions and are essential for life. Cellular polyamine levels are regulated by multiple pathways such as synthesis from amino acid precursors, cellular uptake mechanisms that salvage polyamines from diet and intestinal microorganisms, as well as stepwise degradation and efflux. Investigations using polyamine biosynthetic inhibitors ...

The sphingomyelin-ceramide pathway is an evolutionarily conserved ubiquitous signal transduction system that regulates many cell functions including apoptosis. Sphingomyelin (SM) is hydrolyzed to ceramide by different sphingomyelinases. Ceramide serves as a second messenger in mediating cellular effects of cytokines and stress. In this study, we find that acid sphingomyelinase (SMase) ...

B-cells, triggered via their surface B-cell receptor (BcR), start an apoptotic program known as activation-induced cell death (AICD), and it is widely believed that this phenomenon plays a role in the restriction and focusing of the immune response. Although both ceramide and caspases have been proposed to be involved in ...

P-glycoprotein is a cellular efflux pump. The P-glycoprotein inhibitor PSC 833 causes apoptosis of cancer cells and induces a rise in the intracellular levels of ceramide. Our aims were to determine whether a cause and effect relationship exists between these two actions of PSC 833, and to assess whether the ...

Many papers have shown that sphingolipids control the balance in cells between growth and proliferation, and cell death by apoptosis. Sphingosine-1-phosphate (Sph1P) and glucosylceramide (GlcCer) induce proliferation processes, and ceramide (Cer), a metabolic intermediate between the two, induces apoptosis. In cancers, the balance seems to have come undone and it ...

Biological activities of oxysterols seem tightly regulated. Therefore, the ability to induce cell death of structurally related oxysterols, such as those oxidized at C7(7alpha-, 7beta-hydroxycholesterol, and 7-ketocholesterol), was investigated on U937 cells at different times of treatment in a concentration range of 5-80 microg/ml. Whereas all oxysterols accumulate inside the ...

The primary biochemical consequence of a defect in a gene encoding a functional component of the lysosomal system is disruption of the catabolism or processing of macromolecules in the lumen of the lysosome. Transport of the resulting digestion products through the lysosomal membrane may also be affected. This leads to ...

PURPOSE: To investigate the signal transduction mechanisms involved in the cell death of human retinal pigment epithelial (RPE) cells after their exposure to either hydrogen peroxide (H(2)O(2)) or tri-butyl hydroxperoxide (tBH). METHODS: Cultured human RPE (hRPE) cells were treated with the chemical oxidants tBH and H(2)O(2) as well as with ...

BACKGROUND: Recent evidence suggests that the activation of a non-specific lipid scramblase during apoptosis induces the flipping of sphingomyelin from the cell surface to the cytoplasmic leaftet of the plasma membrane. Inner leaflet sphingomyelin is then cleaved to ceramide by a neutral sphingomyelinase. The production of this non-membrane forming lipid ...

Chromatin-associated phospholipids are well recognized. A report that catalytically active endonuclear CTP:choline-phosphate cytidylyltransferase alpha is necessary for cell survival questions whether endonuclear, CDP-choline pathway phosphatidylcholine synthesis may occur in situ. We report that chromatin from human IMR-32 neuroblastoma cells possesses such a biosynthetic pathway. First, membrane-free nuclei retain all three ...

Stress-induced activation of an acidic sphingomyelinase leading to generation of ceramide, an important lipid mediator, has been associated with apoptosis; however, the implication of this hydrolase has been questioned. The present study aimed at re-evaluating the role of this lysosomal enzyme in apoptosis initiated by different apoptotic inducers. The sensitivity ...

The role of the second messenger ceramide in Fas-mediated death requires clarification. To address this issue, we generated hepatocytes from paired acid sphingomyelinase (ASMase; asmase)(+/+) and asmase(-/-) mice. asmase(-/-) hepatocytes, derived from 8-week-old mice, manifested normal sphingomyelin content and normal morphological, biochemical, and biologic features. Nonetheless, ASMase-deficient hepatocytes did not ...

Fludarabine is used to treat chronic lymphocytic leukemia. Both in vitro and in vivo studies have indicated that apoptosis is an important mode of fludarabine-induced cell death. However, the apoptotic pathways activated are not known. The effects of apoptotic doses of fludarabine on sphingomyelin, ceramide and the production of reactive ...

The mechanism underlying ethanol-induced apoptosis in liver cells is not clear. Sphingomyelin (SM) metabolism is a novel signal transduction pathway that has an impact on apoptosis in many cell types. We investigated whether the SM pathway is involved in ethanol-induced apoptosis in the liver. Hep G2 cells were treated with ...

Regulators of G protein signaling (RGS) proteins accelerate the GTPase activity of Galpha protein subunits in vitro, negatively regulating G protein-coupled receptor signaling. The physiological role of mammalian RGS proteins is largely unknown. The RGS family member rgs2 was cloned as an immediate early response gene up-regulated in T lymphocytes ...

Infantile neuronal ceroid lipofuscinosis (INCL) is a childhood neurodegenerative disease caused by the selective death of cortical neurons and retinal degeneration, as the result of a palmitoyl protein thioesterase 1 (PPT1) deficiency. Recently, we showed that overexpression of PPT1 protects LA-N-5 human neuroblastoma cells against apoptotic death (Cho and Dawson ...

Sphingolipid signaling pathways have been implicated in many critical cellular events. Sphingosine-1-phosphate (SPP), a sphingolipid metabolite found in high concentrations in platelets and blood, stimulates members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors and triggers diverse effects, including cell growth, survival, migration, and morphogenesis. To determine ...

Ceramide is a sphingolipid metabolite that has been implicated in cellular apoptosis and differentiation. It has been shown to induce apoptosis in various mammalian cell lines and, more recently, has been implicated in neuronal apoptosis. Although the mechanisms of ceramide-induced cell death have not been fully elucidated, they appear to ...

In deepwater rice (Oryza sativa), adventitious root primordia initiate at the nodes as part of normal development. Emergence of the roots is dependent on flooding of the plant and is mediated by ethylene action. Root growth was preceded by the induced death of epidermal cells of the node external to ...

Control of lymphocyte cell survival and proliferation is critical for both the immune response and for the prevention of autoimmune and infectious diseases. The actions of interleukin-2, the major T-cell regulatory cytokine, are mediated by the complex network of divergent signalling pathways controlled by its high-affinity receptor. Various studies have ...

Ionizing radiation (IR) induces apoptosis through, in part, cell membrane breakdown signals. Ceramide and diacylglycerol (DAG) are released after IR exposure, which act as second messengers to induce proapoptotic and antiapoptotic signals, respectively. We have previously shown, however, that thyroid cells are relatively resistant to IR-induced apoptosis. To investigate the ...

Bioflavonoids are plant compounds touted for their potential to treat or prevent several diseases including cancers induced by common environmental chemicals. Much of the biologic activity of one such class of pollutants, polycyclic aromatic hydrocarbons (PAH), is mediated by the aryl hydrocarbon receptor/transcription factor (AhR). For example, the AhR regulates ...

BACKGROUND: Ceramides produced by sphingomyelin hydrolysis activate a cycle that is followed by three different major cellular responses: downregulation of cell proliferation, induction of cell differentiation and apoptosis. In the skin, the generation of intracellular ceramide may also provide a link between an extracellular signal and the induction of the ...

Etoposide (VP-16) a topoisomerase II inhibitor induces apoptosis of tumor cells. The present study was designed to elucidate the mechanisms of etoposide-induced apoptosis in C6 glioma cells. Etoposide induced increased formation of ceramide from sphingomyelin and release of mitochondrial cytochrome c followed by activation of caspase-9 and caspase-3, but not ...

Ceramides are the metabolic products of sphingolipids of the eukaryotic cell membranes and are believed to function as signaling molecules in a variety of biological processes. Ceramide induces apoptosis in cultured cardiomyocytes. However, the molecular pathway underlying ceramide-induced apoptosis is not clear. In this study, we investigated the role of ...

Ceramide has been implicated as an important component of radiation-induced apoptosis of human prostate cancer cells. We examined the role of the sphingolipid metabolites--ceramide, sphingosine, and sphingosine-1-phosphate--in susceptibility to radiation-induced apoptosis in prostate cancer cell lines with different sensitivities to gamma-irradiation. Exposure of radiation-sensitive TSU-Pr1 cells to 8-Gy irradiation led ...

Doxorubicin (0.5 microgram/ml) induced caspase-dependent apoptosis in SH-SY5Y neuroblastoma and CHP-100 neuroepithelioma cells. The apoptotic response started to be evident approximately 15 h after drug administration and, as monitored over a 48-h period, was more pronounced in CHP-100 than in SH-SY5Y cells. In both systems, apoptosis was accompanied by elevation ...

The objective of the present study was to evaluate the role of ceramide in mediating apoptosis of dorsal root ganglion neurons induced by either nerve growth factor withdrawal or treatment with the chemotherapeutic agents suramin and cisplatin. Measurement of ceramide accumulation by mass spectrometry and the diacylglycerol kinase assay revealed ...

Ceramide produced by hydrolysis of plasma membrane sphingomyelin (SM) in different cells including brain cells in response to proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta)] plays an important role in coordinating cellular responses to stress, growth suppression, and apoptosis. The present study underlines the importance of IL-10 and IL-13, ...