TY - JOUR
T1 - α-Tocopheryl phosphate
T2 - Uptake, hydrolysis, and antioxidant action in cultured cells and mouse
AU - Nishio, Keiko
AU - Ishida, Noriko
AU - Saito, Yoshiro
AU - Ogawa-Akazawa, Yoko
AU - Shichiri, Mototada
AU - Yoshida, Yasukazu
AU - Hagihara, Yoshihisa
AU - Noguchi, Noriko
AU - Chirico, John
AU - Atkinson, Jeffrey
AU - Niki, Etsuo
N1 - Funding Information:
We thank Dr. Naohiro Goto for technical advice on the measurement of deuterated and unlabeled α-tocopherol by GC–MS. J.A. was supported by an NSERC Discovery Grant.
PY - 2011/6/15
Y1 - 2011/6/15
N2 - α-Tocopheryl phosphate (α-TP), a water-soluble analogue of α-tocopherol, is found in humans, animals, and plants. α-TP is resistant to both acid and alkaline hydrolysis and may exert its own function in this form in vivo. In this study, the uptake, hydrolysis, and antioxidant action of α-TP were measured using α-TP with a deuterated methyl group, CD3, at position 5 of the chroman ring (α-TP(CD3)). The hydrolysis of α-TP(CD3) was followed by measuring α-tocopherol containing the CD3 group, α-T(CD3), in comparison to unlabeled α-tocopherol, α-T(CH3). α-TP(CD3) was incubated with cultured cells, and the intracellular α-T(CD3) formed was measured with HPLC-ECD and GC-MS. α-TP(CD3) was also administered to mice for 4 weeks by mixing in the diet, and α-T(CD3) was measured in plasma, liver, brain, heart, and testis to compare with endogenous unlabeled α-T(CH3). It was found that α-TP(CD3) was taken in and hydrolyzed readily to α-T(CD3) in cultured cells and in mice. The hydrolysis of α-TP(CD3) in cell culture medium was not observed. α-TP protected primary cortical neuronal cells from glutamate-induced cytotoxicity, and α-TP given to mice reduced the levels of lipid peroxidation products in plasma and liver. These results suggest that α-TP is readily hydrolyzed in vivo to α-T, which acts as an antioxidant, and that α-TP may be used as a water-soluble α-T precursor in intravenous fluids, in eye drops, or as a dietary supplement.
AB - α-Tocopheryl phosphate (α-TP), a water-soluble analogue of α-tocopherol, is found in humans, animals, and plants. α-TP is resistant to both acid and alkaline hydrolysis and may exert its own function in this form in vivo. In this study, the uptake, hydrolysis, and antioxidant action of α-TP were measured using α-TP with a deuterated methyl group, CD3, at position 5 of the chroman ring (α-TP(CD3)). The hydrolysis of α-TP(CD3) was followed by measuring α-tocopherol containing the CD3 group, α-T(CD3), in comparison to unlabeled α-tocopherol, α-T(CH3). α-TP(CD3) was incubated with cultured cells, and the intracellular α-T(CD3) formed was measured with HPLC-ECD and GC-MS. α-TP(CD3) was also administered to mice for 4 weeks by mixing in the diet, and α-T(CD3) was measured in plasma, liver, brain, heart, and testis to compare with endogenous unlabeled α-T(CH3). It was found that α-TP(CD3) was taken in and hydrolyzed readily to α-T(CD3) in cultured cells and in mice. The hydrolysis of α-TP(CD3) in cell culture medium was not observed. α-TP protected primary cortical neuronal cells from glutamate-induced cytotoxicity, and α-TP given to mice reduced the levels of lipid peroxidation products in plasma and liver. These results suggest that α-TP is readily hydrolyzed in vivo to α-T, which acts as an antioxidant, and that α-TP may be used as a water-soluble α-T precursor in intravenous fluids, in eye drops, or as a dietary supplement.
KW - Antioxidant
KW - Free radicals
KW - Lipid peroxidation
KW - Oxidative stress
KW - Tocopheryl phosphate
KW - Vitamin E
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U2 - 10.1016/j.freeradbiomed.2011.03.021
DO - 10.1016/j.freeradbiomed.2011.03.021
M3 - Article
C2 - 21443945
AN - SCOPUS:79956119131
VL - 50
SP - 1794
EP - 1800
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 12
ER -