Principles of bioactive lipid signalling: lessons from sphingolipids
- Y. Hannun, L. Obeid
- Biology, Medicine
- Nature Reviews Molecular Cell Biology
- 1 February 2008
An understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action is required to understand the mechanisms of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking. Expand An overview of sphingolipid metabolism: from synthesis to breakdown.
This chapter will pay tribute to the complex regulation of simple sphingolipids, a class of lipids defined by their eighteen carbon amino-alcohol backbones that play significant roles in membrane biology and provide many bioactive metabolites that regulate cell function. Expand Inhibition of Tumor Necrosis Factor-induced Cell Death in MCF7 by a Novel Inhibitor of Neutral Sphingomyelinase*
GW4869 was able, in a dose-dependent manner, to significantly protect from cell death as measured by nuclear condensation, caspase activation, PARP degradation, and trypan blue uptake, therefore localizing N-SMase activation upstream of mitochondrial dysfunction. Expand Programmed cell death induced by ceramide.
The effects of C2-ceramide on DNA fragmentation were prevented by the protein kinase C activator phorbol 12-myristate 13-acetate, which suggests the existence of two opposing intracellular pathways in the regulation of apoptosis. Expand Glutathione Regulation of Neutral Sphingomyelinase in Tumor Necrosis Factor-α-induced Cell Death*
Evidence is provided to demonstrate that depletion of GSH is dependent on activity of interleukin-1β-converting enzyme-like proteases but is upstream of the site of action of Bcl-2 and of the execution phase caspases. Expand Sphingolipids and their metabolism in physiology and disease
- Y. Hannun, L. Obeid
- Biology, Medicine
- Nature Reviews Molecular Cell Biology
- 1 March 2018
These results highlight critical roles for bioactive sphingolipids in most, if not all, major cell biological responses, including all major cell signalling pathways, and they link sphingoipid metabolism to key human diseases. Expand Ceramide synthases at the centre of sphingolipid metabolism and biology.
The function of CerSs as critical regulators of sphingolipid metabolism is discussed, their unique characteristics are highlighted and the emerging roles of Cer Ss in regulating programmed cell death, cancer and many other aspects of biology are explored. Expand Cloning and Characterization of a Saccharomyces cerevisiae Alkaline Ceramidase with Specificity for Dihydroceramide*
It is shown that the two ceramidases in S. cerevisiae have different substrate specificity, such that YPC1p preferentially hydrolyzes phytoceramide, whereas the new ceramidsase YDC1p hydrolyze dihydroceramide preferentialially and phytOCeramide only slightly, suggesting that theTwo enzymes have distinct physiological functions. Expand Thioredoxin Peroxidase Is a Novel Inhibitor of Apoptosis with a Mechanism Distinct from That of Bcl-2*
- Ping Zhang, Bin Liu, San Won Kang, M. Seo, S. Rhee, L. Obeid
- Biology, Medicine
- The Journal of Biological Chemistry
- 5 December 1997
It is demonstrated that when the human TPx II, a member of this family, is stably overexpressed in Molt-4 leukemia cells, it protects from apoptosis induced by serum deprivation, ceramide, or etoposide and may be implicated as an endogenous regulator of apoptosis. Expand