Specific cellular responses to alpha-tocopherol.
In the last 10 years precise cellular functions of alpha-tocopherol, some of which are independent of its antioxidant/radical-scavenging ability, have been revealed. Absorption of alpha-tocopherol from the gut is a selective process. Other tocopherols are not absorbed or are absorbed to a lesser extent. At the post-translational level, alpha-tocopherol inhibits protein kinase C and 5-lipoxygenase and activates protein phosphatase 2A and diacylglycerol kinase. Some genes [platelet glycoprotein IV/thrombospondin receptor/class B scavenger receptor (CD36), alpha-tocopherol transfer protein (alpha-TTP), alpha-tropomyosin, connective tissue growth factor and collagenase] are affected by alpha-tocopherol at the transcriptional level. alpha-Tocopherol also inhibits cell proliferation, platelet aggregation, monocyte adhesion and the oxygen burst in neutrophils. Other antioxidants, such as beta-tocopherol and probucol, do not mimic these effects, suggesting a nonantioxidant, alpha-tocopherol-specific molecular mechanism.
Azzi
A
A
Institute of Biochemistry and Molecular Biology, University of Bern, 3012 Bern, Switzerland.
Breyer
I
I
Feher
M
M
Pastori
M
M
Ricciarelli
R
R
Spycher
S
S
Staffieri
M
M
Stocker
A
A
Zimmer
S
S
Zingg
J M
JM
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019852:Diacylglycerol Kinase / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D016859:Lipoxygenase Inhibitors; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D054648:Protein Phosphatase 2; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*
D016859:Lipoxygenase Inhibitors; D017382:Reactive Oxygen Species; D014810:Vitamin E; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2