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- W4313349713 abstract "Abstract Tocopherol isoforms of vitamin E differentially regulate inflammation and vascular cell adhesion molecule (VCAM)-1 signaling during leukocyte transendothelial migration. During VCAM-1 signaling, tocopherols modulate oxidative activation of protein kinase Cα (PKCα). Although tocopherols are antioxidants, it is not known whether tocopherols also directly regulate PKCα; therefore, we determined whether α-tocopherol and γ-tocopherol directly regulate non-oxidative or oxidative activation of purified PKCα. In a non-oxidative environment, phosphatidylserine (PS)/calcium cofactor-induced PKCα activity was increased by γ-tocopherol but not by α-tocopherol. In contrast, PS-independent oxidative-activation of PKCα was inhibited by α-tocopherol and by 10-fold higher concentrations of γ-tocopherol. In binding studies, lipid vesicles containing α-tocopherol or γ-tocopherol increased binding to the C2 domain (the PS binding domain), but not the C1b domain, of PKCα. To determine direct binding of tocopherols to PKCα in the absence of other lipids, we measured binding of a fluorescent α-tocopherol (NBD-α-tocopherol) to PKCα. Consistent with vesicle binding studies, NBD-α-tocopherol and PS competed for binding to PKCα, indicating that α-tocopherol binds the C2 domain. In summary, α-tocopherol and γ-tocopherol bind the C2 domain of PKCα, but differentially regulate PKCα activity. Therefore, α-tocopherol and γ-tocopherol can function as agonists or antagonists at the C2 domain of PKCα." @default.
- W4313349713 created "2023-01-06" @default.
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- W4313349713 date "2011-04-01" @default.
- W4313349713 modified "2023-09-25" @default.
- W4313349713 title "Vitamin E isoforms directly bind PKCα and differentially regulate PKCα activity. (112.8)" @default.
- W4313349713 doi "https://doi.org/10.4049/jimmunol.186.supp.112.8" @default.
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