Effect of 27-hydroxycholesterol on cellular sphingomyelin synthesis and Ca++ content in cultured smooth muscle cells.
The relationships among sphingomyelin synthesis cytosolic free Ca++ level and cytotoxicity in the presence of 27-hydroxycholesterol were investigated by measurement of [methyl-3H] choline incorporation into sphingomyelin, phosphatidylcholine, phosphocholine and cytidine choline 5'-diphosphate, 45Ca++ uptake, cytosolic free Ca++ levels and viable cell numbers. The results indicated that 27-hydroxycholesterol at higher than normal level induced increased [3H] choline incorporation in sphingomyelin accompanied by decreased radioactivity in phosphatidylcholine but did not alter [3H] choline content in phosphocholine and cytidine choline 5'-diphosphate. The increased radioactivity in sphingomyelin by 27-hydroxycholesterol was detected first, followed by detection of the enhanced Ca++ uptake and cytosolic free Ca++. Finally, a decrease in viable cell number occurred. We suggest that the increased transfer from phosphatidylcholine to sphingomyelin by 27-hydroxycholesterol may be related to enhanced cytosolic free Ca++.
Zhou
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Burnsides Research Laboratory, University of Illinois, Urbana 61801, USA.
Kummerow
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FA
D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured / Q000187:drug effects; D002794:Choline / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D013109:Sphingomyelins / Q000096:biosynthesis*
D006888:Hydroxycholesterols; D010713:Phosphatidylcholines; D013109:Sphingomyelins; C017506:methylcholine; D010767:Phosphorylcholine; D003566:Cytidine Diphosphate Choline; C076996:27-hydroxycholesterol; D002794:Choline; D002118:Calcium