Ceramide pathways modulate ethanol‐induced cell death in astrocytes

• DOI: 10.1046/j.1471-4159.2003.02130.x
• Publication Date: 2010-07-16T06:10:11Z
• Authors: María Pascual; Soraya L. Valles; Jaime Renau‐Piqueras; Consuelo Guerri
• Keywords: 0303 health sciences; Cell Death; Dose-Response Relationship, Drug; Caspase 3; Brain; Central Nervous System Depressants; Enzyme-Linked Immunosorbent Assay; Coatomer Protein; Dinoprostone; Amidohydrolases; 03 medical and health sciences; Animals, Newborn; Astrocytes; Caspases; Ceramidases; Animals; Colorimetry; Drug Interactions; Enzyme Inhibitors; Carrier Proteins; Cells, Cultured; Chromatography, High Pressure Liquid

We showed previously that alcohol exposure during in vivo brain development induced astroglial damage and caused cell death. Because ceramide modulates a number of biochemical cellular responses to stress, including apoptosis, we now investigate whether ethanol-induced death astrocytes is mediated by signalling pathways triggering apoptosis. Here show both ethanol are able induce apoptotic cultured astrocytes, dose-dependent manner, C2-ceramide addition potentiates the effects ethanol. Cell associated with stimulation neutral acidic sphingomyelinase (SMase) generation, as well activation stress-related kinases, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (p38) extracellular signal-regulated (ERK) pathways. also provide evidence for participation JNK death, because pharmacological inhibitors these kinases largely prevent apoptosis or C2-ceramide. Furthermore, ERK triggers cyclo-oxygenase-2 (COX-2) release prostaglandin E2, blockade (MEK)/ERK pathway PD98059 abolishes up-regulation COX-2 plus ceramide, decreases These results strongly suggest stimulate SMase-ceramide pathway, leading implicated findings an insight into mechanisms involved development.