title: Ceramide induces non-apoptotic cell death in human glioma cells.
abstract: Ceramide causes either apoptosis or non-apoptotic cell death depending on model system and experimental conditions. The present study was undertaken to examine the effect of ceramide on cell viability and its molecular events leading to cell death in A172 human glioma cells. Ceramide induced cell death in a dose-dependent manner and the cell death was dependent on generation of reactive oxygen species and lipid peroxidation. TUNEL assay, Hoechst 33258 staining, and flow cytometric analysis did not show typical apoptotic morphological features. Ceramide caused phosphorylation of extracellular signal-regulated kinase (ERK) and p38, but the cell death was not affected by inhibitors of MAPK subfamilies. Ceramide caused ATP depletion without loss of mitochondrial membrane potential. Ceramide did not induce caspase activation and ceramide-induced cell death was also not altered by inhibitors of caspase activation. Transfection of dominant inhibitory mutant of IkappaBalpha (S32A/36A) and pretreatment of pyrrolidinedithiocarbamate, an inhibitor of NF-kappaB, enhanced ceramide-induced cell death. These results indicate that ceramide causes non-apoptotic, caspase-independent cell death by inducing reactive oxygen species generation in A172 human glioma cells. NF-kappaB is involved in the regulation of ceramide-induced cell death in human glioma cells.
authors.affiliation: Department of Neurosurgery, College of Medicine, Pusan National University, 602-739, Pusan, Korea.
authors.forename: Wi Hyun
authors.initials: WH
authors.lastname: Kim
authors.forename: Chang Hwa
authors.initials: CH
authors.lastname: Choi
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Kang
authors.forename: Chae Hwa
authors.initials: CH
authors.lastname: Kwon
authors.forename: Yong Keun
authors.initials: YK
authors.lastname: Kim
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000494:pharmacology*; D004789:Enzyme Activation; D005434:Flow Cytometry; D005910:Glioma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species; D014162:Transfection
chemical_list: D002518:Ceramides; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D017382:Reactive Oxygen Species; D000072000:NF-KappaB Inhibitor alpha; D020169:Caspases