The present study tested the hypotheses that 1) short-term dietary deficiency of magnesium (21 days) in rats would result in the upregulation of sphingomyelin synthase (SMS) and p53 in cardiac and vascular (aortic) smooth muscles, 2) low levels of Mg(2+) added to drinking water would either prevent or greatly reduce the upregulation of both SMS and p53, 3) exposure of primary cultured vascular ...

We previously reported that ceramide synthase 6 (CerS6) is elevated in response to folate stress in cancer cells, leading to enhanced production of C16-ceramide and apoptosis. Antifolate methotrexate (MTX), a drug commonly used in chemotherapy of several types of cancer, is a strong inhibitor of folate metabolism. Here we investigated whether this drug targets CerS6. We observed that CerS6 prot...

The sphingomyelin (SM) pathway is a ubiquitous, evolutionarily conserved signalling system analogous to conventional systems such as the cAMP and phosphoinositide pathways. Ceramide, which serves as second messenger in this pathway, is generated from SM by the action of a neutral or acidic SMase, or by de novo synthesis co-ordinated through the enzyme ceramide synthase. A number of direct targe...

Microcystin-LR (MCLR) is one of the most common and most toxic members of the microcystins, which cause serious environmental disasters worldwide. Although the major toxicity of MCLR has been ascribed to its potent ability to inhibit protein phosphatase 1 and protein phosphatase 2A (PP2A), recent studies have suggested that MCLR may also perturb other important cellular processes, such as gener...

Inhibitors of sphingolipid metabolism are frequently used to investigate the role of ceramide and other sphingolipids as intracellular signaling molecules. For example, the inhibitor of glucosylceramide synthase D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) is commonly used to deplete glycosphingolipids and increase ceramide levels. Ceramide is known to induce growth arrest an...

This work describes two unusual features of membrane development in a eukaryotic cell. (a) The induction of an extensive network of tubovesicular membranes by the malaria parasite Plasmodium falciparum in the cytoplasm of the mature erythrocyte, and its visualization with two ceramide analogues C5-DMB-ceramide and C6-NBD-ceramide. "Sectioning" of the infected erythrocytes using laser confocal m...

The prevailing mechanisms of action of traditional chemotherapeutic agents have been challenged by sphingolipid cancer research. Many studies have shown that ceramide generation in response to cytotoxic agents is central to tumor cell death. Ceramide can be generated either via hydrolysis of cell-membrane sphingomyelin by sphingomyelinases, hydrolysis of cerebrosides, or via de novo synthesis b...