Lactic acidosis stimulates ganglioside and ceramide generation without sphingomyelin hydrolysis in rat cortical astrocytes.
Acidosis is a ubiquitous feature of cerebral ischemia, and triggers a cascade of biochemical events that results in neuronal injury. The purpose of this study was to evaluate the effects of lactic acidosis on the ganglioside composition, the ceramide and sphingomyelin (SM) levels in rat cortical astrocytes. Primary astrocyte cultures were exposed to lactic acid (pH 5.5) for 2, 5 and 17 h, and cell death was evaluated at each time point. Gangliosides, ceramides and SM were analyzed by high-performance thin layer chromatography. Lactic acidosis caused a progressive increase of both GM3 and GD3 gangliosides up to 5 h of treatment. However, at 17 h of acidosis, GM3 tented to return to the normal level whereas GD3 accumulated. Additionally, ceramides were gradually generated, whereas no significant decrease of SM occured for 17 h of acidosis. These results suggest that ceramides were not produced by the breakdown of SM and may be served as metabolic precursor for the biosynthesis of GM3 and GD3. Since these lipids are important messengers of the adaptative responses to stress, accumulation of sphingolipids triggered by lactic acid exposure of astrocytes might play an important role in determining the outcomes of injurious processes.
Barrier
Laurence
L
Groupe de Recherche sur le Vieillissement Cérébral, GReViC EA 3808, Faculté de Médecine et de Pharmacie, 34, rue du Jardin des Plantes, BP 199, 86005 Poitiers Cedex, France. lbarrier@univ-poitiers.fr
Ingrand
Sabrina
S
Piriou
Alain
A
Touzalin
Antoine
A
Fauconneau
Bernard
B
D000140:Acidosis, Lactic / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005732:Gangliosides / Q000378:metabolism*; D006868:Hydrolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013109:Sphingomyelins / Q000378:metabolism*
D002518:Ceramides; D005732:Gangliosides; D013109:Sphingomyelins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases