The formation of ceramide from sphingomyelin is associated with cellular apoptosis

• Autorzy: Dawson G. , Goswami R. , Kilkus J. , Wiesner D.
• Języki publikacji: EN

Abstrakty

EN

The apoptotic response of the immature B-cell to the cross-linking of surface IgM receptors provides a good model for cell death and we show in WEHI-231 B-cells that the time course of apoptosis corresponds to the increased formation of ceramide, as measured either by mass (using the diacylglycerol kinase method) or radiolabelling with [3H]palmitate. Inhibitors of sphingosine biosynthesis have no effect on cell death induced by anti-IgM in WEHI-231 but inhibitors of ceramidase accelerate apoptosis, suggesting that activation of sphingomyelinase is the key event in apoptosis. We have demonstrated this by in vitro assay of neutral sphingomyelinase. Apoptosis is also important in normal brain development and neuronal survival is dependent upon phosphatidylinositol 3-kinase (PI3-kinase) activation by growth factors (insulin, nerve growth factor etc.). Withdrawal of these growth factors or inhibition of PI3-kinase with wortmannin or LY294002 activated the pro-apoptotic CPP32 (Yama/Apopain/caspase 3, EC 3.4.22), activated neutral sphingomyelinase and increased ceramide formation in an immortalized dorsal root ganglion cell line F-11. Protection against apoptosis can be achieved by overexpression of the bcl2 family of proteins or addition of drugs which elevate cAMP levels. cAMP protects against apoptosis induced by either wortmannin or staurosporine. The specificity for cAMP was confirmed by showing protection with the specific agonist (Sp)cAMPS and increased killing with the antagonist (Rp)cAMPS. However, cAMP did not protect against ceramide killing, suggesting that there are at least two major pathways of apoptosis in neuronal cells.

Słowa kluczowe

EN

ceramide; neuronal cell; kinase inhibitor; sphingomyelin; growth factor; in vitro; cellular apoptosis; apoptosis; cell culture; staurosporine; phosphatidylinositol 3-kinase

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1998
• Tom: 45
• Numer: 2
• Opis fizyczny: p.287-297,fig.

Twórcy

autor

Dawson G.

• University of Chicago, 5841 S.Maryland Ave., Chicago, IL 60637, USA

autor

Goswami R.

autor

Kilkus J.

autor

Wiesner D.

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