The sphingolipid ceramide mediates various cellular processes in response to several extracellular stimuli. Some genotoxic stresses are able to induce p53-dependent ceramide accumulation leading to cell death. However, in other cases, in the absence of the tumor suppressor protein p53, apoptosis proceeds partly due to the activity of this "tumor suppressor lipid", ceramide. In the current revie...

Abstract Ceramide kinase (CERK) phosphorylates ceramide to produce ceramide-1-phosphate (C1P), which is involved in the development of metabolic inflammation. TNF-? modulates inflammatory responses monocytes associated with various disorders; however, underlying mechanisms remain not fully understood. Here, we investigated role CERK TNF-?-induced monocytes. Our results show that disruption acti...

Ceramide has been implicated to play an important role in the cell signaling pathway involved in apoptosis. Most studies that have used the apoptotic model of cellular injury have suggested that enhanced ceramide generation is the result of the breakdown of sphingomyelin by sphingomyelinases. However, the role of ceramide synthase in enhanced ceramide generation in response to oxidant stress ha...

Liu, Gele, Leonard Kleine, Rania Nasrallah, and Richard L. Hébert. Bradykinin inhibits ceramide production and activates phospholipase D in rabbit cortical collecting duct cells. Am. J. Physiol. 276 (Renal Physiol. 45): F589–F598, 1999.—Recent reports suggest that inflammatory cytokines, growth factors, and vasoconstrictor peptides induce sphingomyelinase (SMase) activity. This results in the h...

Recent evidence suggests that the ability of ceramides to induce apoptosis is due to a direct action on mitochondria. Mitochondria are known to contain enzymes responsible for ceramide synthesis and hydrolysis and mitochondrial ceramide levels have been shown to be elevated prior to the mitochondrial phase of apoptosis. Ceramides have been reported to induce the release of intermembrane space p...

Ceramide is a sphingolipid that serves as an important second messenger in an increasing number of stress-induced pathways. Ceramide has long been known to affect the mitochondria, altering both morphology and physiology. We sought to assess the impact of ceramide on skeletal muscle mitochondrial structure and function. A primary observation was the rapid and dramatic division of mitochondria i...

Ceramide functions as a growth-inhibitory lipid-signalling molecule and might have a role in mediating the effects of extracellular agents on cell growth, differentiation and senescence. Here we investigate the roles of ceramide in cell cycle progression. With the use of the model of serum withdrawal, we were able to synchronize Wi-38 human diploid fibroblasts at different stages of cell cycle....

Resistance to chemotherapy is the major cause of cancer treatment failure. Insight into the mechanism of action of agents that modulate multidrug resistance (MDR) is instrumental for the design of more effective treatment modalities. Here we show, using KB-V-1 MDR human epidermoid carcinoma cells and [3H]palmitic acid as metabolic tracer, that the MDR modulator SDZ PSC 833 (PSC 833) activates c...

BACKGROUND/AIMS Major depressive disorder is one of the most common diseases in western countries. The disease is mainly defined by its psychiatric symptoms. However, the disease has also many symptoms outside the central nervous system, in particular cardiovascular symptoms. Recent studies demonstrated that the acid sphingomyelinase/ceramide system plays an important role in the development of...

Title of Dissertation: CERAMIDE CHANNELS AND THE INDUCTION OF APOPTOSIS: STRUCTURAL INSIGHTS ON CHANNEL FORMATION AND REGULATION BY BCL-2 FAMILY PROTEINS. Meenu Nadisha Perera, Doctor of Philosophy, 2012 Directed by: Professor Marco Colombini Department of Biology A critical event in apoptosis is the release of intermembrane space proteins from mitochondria following mitochondrial outer membran...