Induction of intracellular ceramide by interleukin-1 beta in oligodendrocytes.
The sphingomyelin pathway has been implicated in mediating the effect of several extracellular agents leading to important biochemical and cellular changes. The aim of this investigation is to study interleukin-1 beta (IL-1 beta) signaling in oligodendrocytes. For this purpose, the CG4 oligodendrocyte cells were differentiated and incubated with IL-1 beta. This treatment induced a time- and dose-dependent increase of the endocellular ceramide. To mimic the effect of the elevation of endogenous ceramide, the CG4 cells were treated with the ceramide analogue C2-ceramide. Cell survival, measured with the MTT assay, showed that, by increasing the concentration of ceramide, up to 40% of CG4 cells were dying within 6 h, similar data were obtained with the primary differentiated oligodendrocytes. Condensation of chromatin, nuclear fragmentation, and formation of apoptotic bodies indicated that apoptosis was the cause of death. Surprisingly, long-term exposure (72 h) to increasing concentrations of IL-1 beta, which increases intracellular ceramide, did not induce oligodendroglial cell death. These results show that an increase of intracellular ceramide is not sufficient to induce apoptosis in oligodendrocytes and that IL-1 beta signaling through the ceramide pathway in these cells can mediate functions other than programmed cell death.
Brogi
A
A
Istituto Biologia Generale Università di Siena, Italy.
Strazza
M
M
Melli
M
M
Costantino-Ceccarini
E
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism*; D002843:Chromatin / Q000737:chemistry / Q000502:physiology; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000737:chemistry; D008722:Methods; D009836:Oligodendroglia / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013109:Sphingomyelins / Q000378:metabolism; D013194:Staining and Labeling; D013778:Tetrazolium Salts / Q000032:analysis; D013844:Thiazoles / Q000032:analysis; D013997:Time Factors
D002518:Ceramides; D002843:Chromatin; D004396:Coloring Agents; D007375:Interleukin-1; D011994:Recombinant Proteins; D013109:Sphingomyelins; D013778:Tetrazolium Salts; D013844:Thiazoles; C065576:ceramide 1-phosphate; C022616:thiazolyl blue