Increases in Ceramide Levels in Normal Human Mesangial Cells Subjected to Different Cellular Stresses Result from Changes in Distinct Enzyme Activities and Can Influence Cellular Responses to Other Stimuli

Sphingolipids, ceramide in particular, have come to be regarded as having roles in cellular signaling, most recently being associated with stress and the cellular responses to stress. In the present study we first examined the mechanisms involved in the changes in cellular ceramide levels in normal...

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Bibliographic Details
Published in:Journal of biochemistry (Tokyo) 1999-04, Vol.125 (4), p.737-745
Main Authors: Sweeney, Elizabeth A., Igarashi, Yasuyuki
Format: Article
Language:English
Subjects:
Amidohydrolases - metabolism
apoptosis
Apoptosis - drug effects
Cell Count
Cell Division - drug effects
Cells, Cultured
Ceramidases
ceramide
Ceramides - metabolism
Glomerular Mesangium - cytology
Glomerular Mesangium - enzymology
Glomerular Mesangium - metabolism
Growth Substances - pharmacology
Humans
mesangial cell
N-dimethylsphingosine
Sphingomyelin Phosphodiesterase - metabolism
Sphingosine - pharmacology
stress
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Summary:Sphingolipids, ceramide in particular, have come to be regarded as having roles in cellular signaling, most recently being associated with stress and the cellular responses to stress. In the present study we first examined the mechanisms involved in the changes in cellular ceramide levels in normal human mesangial cells (NHMC) in the growth, quiescent, and senescent phases as well as those resulting from environmental stimuli. We found that in NHMC total ceramide levels increase in response to cellular stresses as a result of a combination of enzyme activities. Furthermore, different stresses cause different alterations in various enzyme activities, with age and growth influencing acidic enzymes, but cell density affecting neutral, resulting in final ceramide level increases which most likely are associated with distinct pools of ceramide. Secondly, we examined the influence of changes in ceramide levels on apoptosis induced by sphingosine and its methylated derivative N,N-dimethylsphingosine. We found that increases in cellular ceramide levels prohibited the apoptosis and caused a quiescent state in the cells. The data presented here provide additional insight into the roles of ceramide and related enzymes in cellular responses to stress and suggest a possible relevance to in vivo disease states.
ISSN:0021-924X
DOI:10.1093/oxfordjournals.jbchem.a022344