REVIEW: Functions of Sphingosine in Cell Proliferation and Death

A. V. Alessenko

Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 117977 Russia; fax: (095) 137-4101; E-mail: aless@center.chph.ras.ru

Submitted July 25, 1997

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Interest in the biological functions of sphingosine, the metabolic product of sphingolipids, increased dramatically during the last few years. Sphingosine was found to be an exogenous inhibitor of protein kinase C and of many cell functions which depend on this enzyme including cell proliferation, differentiation, and programmed death. Sphingosine also activates some other protein kinases and regulates a variety of enzymes which are involved in the transmission of cell signals. Sphingosine mobilizes Ca²⁺ from intracellular stores and controls the specific Ca²⁺-channel. Sphingosine influences the synthesis of DNA and interacts with DNA in competition for the binding sites with histones, some enzymes, and transcriptional factors. Sphingosine is suggested to be a second messenger in the transmission of cell proliferation and apoptosis signals. The possible use of sphingosine in combined treatment of various diseases as a synergist of many drugs is considered.

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KEY WORDS: sphingosine, cell proliferation, apoptosis, DNA synthesis, gene expression, nucleus, protein kinases, Ca²⁺ mobilization, signal transmission

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