Modulation of cell proliferation and gene expression by alpha-tocopheryl phosphates: relevance to atherosclerosis and inflammation.
The effect of a mixture of alpha-tocopheryl phosphate and di-alpha-tocopheryl phosphate (TPm) was studied in vitro on two cell lines, RASMC (from rat aortic smooth muscle) and human THP-1 monocytic leukaemia cells. Inhibition of cell proliferation by TPm was shown in both lines and occurred with TPm at concentrations lower than those at which alpha-tocopherol was equally inhibitory. TPm led in non-stimulated THP-1 cells to inhibition of CD36 mRNA and protein expression, to inhibition of oxidized low density lipoprotein surface binding and oxLDL uptake. In non-stimulated THP-1 cells, alpha-tocopherol had only very weak effects on these events. Contrary to alpha-tocopherol, TPm was cytotoxic to THP-1 cells at high concentrations. Thus, TPm is able to inhibit the major aggravating elements involved in the progression of atherosclerosis. The higher potency of TPm may be due to a better uptake of the molecule and to its intracellular hydrolysis, providing more alpha-tocopherol to sensitive sites. Alternatively, a direct effect of the phosphate ester on specific cell targets may be considered.
Munteanu
Adelina
A
Institute of Biochemistry and Molecular Biology, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.
Zingg
Jean-Marc
JM
Ogru
Esra
E
Libinaki
Roksan
R
Gianello
Robert
R
West
Simon
S
Negis
Yesim
Y
Azzi
Angelo
A
D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053938:DNA Fragmentation; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000494:pharmacology*
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; C012552:alpha-tocopherol phosphate; D024502:alpha-Tocopherol