Long-chain carboxychromanols are the major metabolites of tocopherols and tocotrienols in A549 lung epithelial cells but not HepG2 cells
2005
You, C.S. | Sontag, T.J. | Swanson, J.E. | Parker, R.S.
Human lung type II cell derived A549 epithelial cancer cells and HepG2 hepatocytes constitutively express cytochrome P4504F2, a P450 we previously identified as a tocopherol-[omega]-hydroxylase. To determine if A549 cells would metabolize tocochromanols via the [omega]-hydroxylase pathway, we compared the metabolism of tocopherols ([alpha]-, [gamma]-, [delta]-TOH) and tocotrienols ([alpha]-, [gamma]-, [delta]-T3) in these 2 cell lines. Cultures were incubated with [alpha]-, [gamma]-, or [delta]-TOH, or the analogous T3s, and synthesis of their metabolites quantitated by GC-MS. A549 cells metabolized all tocochromanols 2-3 times more extensively than HepG2 cells (P < 0.001) except [alpha]-TOH, a difference not related to cell uptake of substrate but rather was reflective of greater microsomal TOH-[omega]-hydroxylase enzyme activity. Notably, 9'-carboxychromanols were the major metabolites of all [gamma]- and [delta]-TOHs and T3s in A549 cultures, whereas 3'- and 5'-carboxychromanols predominated in HepG2 cultures. Accumulation of 9'-carboxychromanols in A549 cultures was due to their inefficient conversion to 7'-carboxychromanols relative to HepG2 cells. Sesamin inhibited tocochromanol metabolism in both cells types, and neither cell type exhibited evidence of alternative (sesamin-insensitive) pathways of metabolism. TOH-[omega]-hydroxylase activity was undetectable in rat primary lung type II cells, suggesting that expression of activity was associated with transformation of normal type II cells to cancer cells. Long-chain carboxychromanol metabolites of [gamma]-TOH and other forms of vitamin E can be biosynthesized in A549 cultures for assessment of their biological activity, including their potential inhibition of synthesis of inflammatory mediators.
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