We investigated the possibility of the proapoptotic lipid ceramide as an indicator of chemoresistance in leukemia. Doxorubicin (DOX) increased the ceramide level and apoptosis in drug-sensitive HL-60 cells but not in drug-resistant HL-60/ADR cells, under the condition that the uptake of DOX was not different between the two cell lines. In addition, exogenous N-acetylsphingosine (C2-ceramide) en...

Angiostatin is a cleavage product of plasminogen that has anti-angiogenic properties. We investigated whether the effects of angiostatin on endothelial cells are mediated by ceramide, a lipid implicated in endothelial cell signaling. Our results demonstrate that angiostatin produces a transient increase in ceramide that correlates with actin stress fiber reorganization, detachment and death. DN...

Free ceramide, glucosylceramide, and sphingomyelin were isolated from mature cells of adult rat small intestine. Free ceramide and ceramide cleaved from sphingomyelin by enzymatic hydrolysis were fractionated by thin-layer chromatography on borate-impregnated silica gel plates. Sphingoid bases were characterized by gas-liquid chromatography of aldehydes formed upon periodate oxidation. Fatty ac...

It is now well established that glycerophospholipids and their metabolic products (such as diacylglycerol (DAG), inositol trisphosphate, eicosanoids, and platelet-activating factor) function in signal transduction and cell regulation (14). On the other hand, a role for membrane sphingolipids in signal transduction has not been well appreciated although sphingolipids exhibit even greater structu...

Tumor necrosis factor (TNF) signals cell death and simultaneously induces generation of ceramide. To evaluate the contribution of ceramide to TNF-dependent cell death, we generated clones of the TNF-sensitive cell line L929 that constitutively overexpress human acid ceramidase (AC). Ceramidase, in concert with sphingosine kinase, metabolizes ceramide to sphingosine-1-phosphate (SPP), an inducer...

Helicobacter pylori adheres to gastric epithelial cells and stimulates interleukin-8 production. Ceramide, a lipid second messenger, has become known as an important mediator of some actions of several cytokines. We have recently reported that H. pylori-dependent ceramide production may activate nuclear factor-kappaB and mediate interleukin-8 expression in human gastric cancer cell lines. In th...

Although mechanisms involved in the pathogenesis of asthma remain unclear, roles for oxidative/nitrosative stress, epithelial cell apoptosis, and airway inflammation have been documented. Ceramide is a sphingolipid with potent proinflammatory and proapoptotic properties. This study aimed at determining whether increased formation of ceramide contributes to the development of airway inflammation...

Ceramide, a bioactive membrane sphingolipid, functions as an important second messenger in apoptosis and cell signaling. In response to stresses, it may be generated by de novo synthesis, sphingomyelin hydrolysis, and/or recycling of complex sphingolipids. It is cleared from cells through the activity of ceramidases, phosphorylation to ceramide-1-phosphate, or resynthesis into more complex sphi...

Ceramide-activated NAD(P)H oxidase has been reported to participate in homocysteine (Hcys)-induced abnormal metabolism of the extracellular matrix (ECM) in rat glomerular mesangial cells. However, it remains unknown whether this ceramide-redox signaling pathway contributes to glomerular injury induced by hyperhomocysteinemia (hHcys) in vivo. The present study was designed to address this questi...

Ceramide signaling plays an important role in tumor progression and development of chemoresistance, and ceramide-based therapies are proposed as potential therapeutic tools for the treatment of breast cancer. We investigated the effect of exogenous ceramide on the cell cycle progression of MCF-7 breast cancer cells. Ceramide induced a selective arrest of MCF-7 cells in the G1-phase, which was a...