Negative regulation of interleukin‐1β‐activated neutral sphingomyelinase by protein kinase C in rat mesangial cells

FEBS Letters

Pfeilschifter, Josef²  van den Bosch, Henk¹  Kaszkin, Marietta²  Huwiler, Andrea²  Scholz, Kirsten² 

[1] Center for Biomembranes and Lipid Enzymology, University of Utrecht, NL-3584 CH Utrecht, The Netherlands;Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany

关键词: Ceramide;    Mesangial cell;    Phorbol ester;    Protein kinase C;    Sphingomyelinase;   

DOI  :  10.1016/S0014-5793(98)01445-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Endogenous ceramide is produced by the action of acidic or neutral sphingomyelinases (SMase) in response to stimuli such as proinflammatory cytokines or other inducers of stress. Interleukin-1β (IL-1β) is known to stimulate ceramide formation in rat renal mesangial cells; however, the respective subtype of SMase and its regulation have not been investigated. We found that IL-1β induced an increase in endogenous ceramide levels via the action of a neutral SMase but not an acidic SMase in rat mesangial cells. Cytokine-induced activation of neutral SMase was inhibited by stimulation of protein kinase C (PKC) by the phorbol ester TPA which caused a reduction of ceramide back to control levels. This inhibitory effect of TPA was reversed by the specific PKC-inhibitor Ro-318220. Long-term incubation (24 h) of mesangial cells with TPA, which downregulates PKC-α, -δ, and -ϵ isoenzymes, resulted in a recovery of IL-1β-stimulated neutral SMase activity as well as ceramide formation. These data implicate an important modulatory function of PKC in ceramide production in IL-1β-activated mesangial cells.

【 授权许可】

Unknown