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Review
. 2002 Jul;110(1):3-8.
doi: 10.1172/JCI16127.

The therapeutic potential of modulating the ceramide/sphingomyelin pathway

Richard Kolesnick  1
Affiliations
Review

The therapeutic potential of modulating the ceramide/sphingomyelin pathway

Richard Kolesnick. J Clin Invest. 2002 Jul.
No abstract available

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Figures

Figure 1
Figure 1
Schematic representation of sphingolipid intermediary metabolism.
Figure 2
Figure 2
A model for Fas-induced capping through ASMase activation. Ligation of preformed Fas trimers on a target cell by transmembrane Fas ligand (FasL) activates small amounts of caspase-8 within the cytoplasm of that cell, which is nonetheless sufficient to induce ASMase translocation into membrane rafts. The consequent hydrolysis of SM to ceramide, which self-associates, initiates coalescence of ceramide-enriched rafts into larger patches (isolated ovals) and platforms (aggregated ovals). Only ligated Fas can enter and concentrate within these platforms, permitting oligomerization of the downstream Fas effectors FADD and caspase-8 (not shown), the constituents of the death-inducing signaling complex (DISC). The extent to which this raft reorganization system is used for Fas signaling is currently unknown. Fas may not be the only cell surface receptor to employ this concentrating system, as a recent study suggests that CD40 may also cap in ceramide-rich platforms (61). Note that the transmembrane domains of some, and the cytoplasmic domain of all, Fas molecules are not depicted in this schematic for reasons of clarity. Similarly, the FasL-presenting cell is only shown once (upper left). PM, plasma membrane.
Figure 3
Figure 3
C6-ceramide limited neointimal hyperplasia after balloon angioplasty in rabbit carotid arteries. (a–c) Hematoxylin and eosin–stained sections from excised arteries 2 weeks after angioplasty. (a) Sham-treated control artery. (b) Artery treated with a balloon coated with DMSO/ethanol (1:1, vol/vol) displays marked neointimal hyperplasia. (c) Artery treated with a C6-ceramide–coated balloon displays minimal neointimal hyperplasia. Bar, 200 μm. Reprinted with permission (49).
See this image and copyright information in PMC

References

    1. Kolesnick RN. Sphingomyelin and derivatives as cellular signals. Prog Lipid Res. 1991;30:1–38. - PubMed
    1. Kolesnick RN. 1,2-Diacylglycerols but not phorbol esters stimulate sphingomyelin hydrolysis in GH3pituitary cells. J Biol Chem. 1987;262:16759–16762. - PubMed
    1. Kolesnick RN, Clegg S. 1,2-Diacylglycerols, but not phorbol esters, activate a potential inhibitory pathway for protein kinase C in GH3pituitary cells: evidence for involvement of a sphingomyelinase. J Biol Chem. 1988;263:6534–6537. - PubMed
    1. Kolesnick RN. Sphingomyelinase action inhibits phorbol ester-induced differentiation of human promyelocytic leukemic (HL-60) cells. J Biol Chem. 1989;264:7617–7623. - PubMed
    1. Okazaki T, Bell RM, Hannun Y. Sphingomyelin turnover induced by vitamin D3in HL-60 cells: role in cell differentiation. J Biol Chem. 1989;264:19076–19080. - PubMed

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