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KMID : 0043320080310010054
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Archives of Pharmacal Research
2008 Volume.31 No. 1 p.54 ~ p.59
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N,N-Dimethyl-D-erythro-Sphingosine Increases Intracellular Ca2+ Concentration via Na+-Ca2+ -Exchanger in HCT116 Human Colon Cancer Cells
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Kim Hyo-Lim
Im Dong-Soon
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Abstract
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N,N-dimethyl-D-erythro-sphingosine (DMS), an N-methyl derivative of sphingosine, is an inhibitor of protein kinase C (PKC) and sphingosine kinase (SK). In previous reports, DMS-induced intracellular Ca2+ increase concentration Ca2+ was studied in T lymphocytes, monocytes, astrocytes and neuronal cells. In the present study, we studied DMS-induced increase of Ca2+ in HCT116 human colon cancer cells. We found that the DMS-induced increase of Ca2+ in colon cancer cells is composed of Ca2+ release from intracellular Ca2+ stores and subsequent Ca2+ influx. The Ca2+ release is not related to modulation of inositol 1,4,5-trisphosphate (IP3) receptor or ryanodine receptor. On the other hand, the influx is mediated largely through Ca2+ channels sensitive to verapamil, nifedipine, Ga3+, and La3+. Furthermore, we found that the response is inhibited by bepridil and Ni2+, specific inhibitors of -exchanger, suggesting involvement of Na+-Ca2+ exchanger in the DMS-induced Ca2+ increase in colon cancer cells. This inhibition was also observed in U937 monocytes, but not in 1321N1 astrocytes.
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KEYWORD
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Colon cancer, Calcium, Dimethylsphingosine, Na+-Ca2+ -Exchanger, Signaling
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