|Merrill Jr, A|
|Voss, Kenneth - Ken|
Submitted to: Journal of Toxicology and Applied Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/13/1996
Publication Date: N/A
Citation: N/A Interpretive Summary: Sphingolipids are a type of fat named for their enigmatic ("Sphinx-like") properties. Although still an elusive class of fats, research on the involvement of sphingolipids in the processes which control cell growth, the fate and function of cells, and cell death has been rapidly expanding our understanding of these fats. Many of these fats are altered by cellular metabolism and become very active inside cells. They can act to turn on and turn off processes which are very important to the function of the cells. Recently several toxins have been discovered which occur naturally in corn and other plants which can alter the way these fats are metabolized by both plant and animal cells. Several animal and plant diseases have been found which are caused by these changes. These recent findings illustrate how an understanding of the function of sphingolipids can help solve questions in toxicology and this is undoubtedly only the beginning of this story. Increased understanding of how these toxins alter cell behavior has provided new insights into how the animal and plant diseases which they cause might be reduced or eliminated.
Technical Abstract: The "sphingosin" backbone of sphingolipids was so named by J.L.W. Thudichum in 1884 for its enigmatic ("Sphinx-like") properties. Although still an elusive class of lipids, research on the involvement of sphingolipids in signal transduction pathways that mediate cell growth, differentiation, multiple cell functions, and cell death has been rapidly expanding our understanding of these compounds. In addition to the newly discovered rol of ceramide as an intracellular second messenger for TNFalpha, IL1beta, and other cytokines, sphingosine, sphingosine-1phosphate and other sphingolipid metabolites have recently been demonstrated to modulate cellular calcium homeostasis and cell proliferation. Perturbation of sphingolipid metabolism using synthetic and naturally occurring inhibitors of key enzymes of the biosynthetic pathways is aiding the characterization of these processes, for example: inhibition of cerebroside synthase has indicated a role for ceramide in cellular stress responses including heat shock, and inhibition of ceramide synthase (by fumonisins) has revealed the role of disruption of sphingolipid metabolism in several animal diseases. These findings illustrate how an understanding of the function of sphingolipids can help solve questions in toxicology and this is undoubtedly only the beginning of this story.