Abstract
Although all forms of vitamin E are absorbed, the liver preferentially secretes α-, but not γ-tocopherol, into plasma. Liver α-tocopherol secretion is under the control of the α-tocopherol transfer protein (TTP). Therefore, to assess γ-tocopherol bioactivities Ttpa-/-, +/- and +/+ mice were fed for 5 weeks diets containing γ-tocopherol 550 (γ-T550), γ-tocopherol 60 (γ-T60) mg/kg that also contained trace amounts of α-tocopherol, a vitamin E-deficient diet, or a control diet. Plasma and tissues from mice fed γ-T550 diets were found to contain similar γ- and α-tocopherol concentrations despite the high dietary γ-tocopherol content; nervous tissues contained almost no γ-tocopherol. Liver vitamin E metabolites (carboxyethyl hydroxychromans, CEHCs) were also measured. In mice with widely ranging liver α- (from 0.7 to 16 nmol/g) and γ-tocopherol concentrations (0 to 13 nmol/g), hepatic α-CEHC was undetectable, but γ-CEHC concentrations (0.1 to 0.8 nmol/g) were correlated with both α- and γ-tocopherol concentrations (P < 0.004). Hepatic cytochrome P450s (CYPs) involved in vitamin E metabolism, Cyp4f and Cyp3a, were also measured. There were no variations in Cyp4f protein expression as related to diet or mouse genotype. However, Cyp3a was correlated (P < 0.0001) with liver α-, but not γ-tocopherol concentrations. These data support the hypothesis that α-tocopherol modulates xenobiotic metabolism by increasing Cyp3a expression, γ-CEHC formation, and the excretion of both γ-tocopherol and γ-CEHC.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 773-785 |
| Number of pages | 13 |
| Journal | Free Radical Biology and Medicine |
| Volume | 38 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2005 |
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ASJC Scopus subject areas
- Medicine(all)
- Toxicology
- Clinical Biochemistry
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α-tocopherol modulates Cyp3a expression, increases γ-CEHC production, and limits tissue γ-tocopherol accumulation in mice fed high γ-tocopherol diets. / Traber, Maret G.; Siddens, Lisbeth K.; Leonard, Scott W.; Schock, Bettina; Gohil, Kishorchandra; Krueger, Sharon K.; Cross, Carroll E; Williams, David E.
In: Free Radical Biology and Medicine, Vol. 38, No. 6, 15.03.2005, p. 773-785.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - α-tocopherol modulates Cyp3a expression, increases γ-CEHC production, and limits tissue γ-tocopherol accumulation in mice fed high γ-tocopherol diets
AU - Traber, Maret G.
AU - Siddens, Lisbeth K.
AU - Leonard, Scott W.
AU - Schock, Bettina
AU - Gohil, Kishorchandra
AU - Krueger, Sharon K.
AU - Cross, Carroll E
AU - Williams, David E.
PY - 2005/3/15
Y1 - 2005/3/15
N2 - Although all forms of vitamin E are absorbed, the liver preferentially secretes α-, but not γ-tocopherol, into plasma. Liver α-tocopherol secretion is under the control of the α-tocopherol transfer protein (TTP). Therefore, to assess γ-tocopherol bioactivities Ttpa-/-, +/- and +/+ mice were fed for 5 weeks diets containing γ-tocopherol 550 (γ-T550), γ-tocopherol 60 (γ-T60) mg/kg that also contained trace amounts of α-tocopherol, a vitamin E-deficient diet, or a control diet. Plasma and tissues from mice fed γ-T550 diets were found to contain similar γ- and α-tocopherol concentrations despite the high dietary γ-tocopherol content; nervous tissues contained almost no γ-tocopherol. Liver vitamin E metabolites (carboxyethyl hydroxychromans, CEHCs) were also measured. In mice with widely ranging liver α- (from 0.7 to 16 nmol/g) and γ-tocopherol concentrations (0 to 13 nmol/g), hepatic α-CEHC was undetectable, but γ-CEHC concentrations (0.1 to 0.8 nmol/g) were correlated with both α- and γ-tocopherol concentrations (P < 0.004). Hepatic cytochrome P450s (CYPs) involved in vitamin E metabolism, Cyp4f and Cyp3a, were also measured. There were no variations in Cyp4f protein expression as related to diet or mouse genotype. However, Cyp3a was correlated (P < 0.0001) with liver α-, but not γ-tocopherol concentrations. These data support the hypothesis that α-tocopherol modulates xenobiotic metabolism by increasing Cyp3a expression, γ-CEHC formation, and the excretion of both γ-tocopherol and γ-CEHC.
AB - Although all forms of vitamin E are absorbed, the liver preferentially secretes α-, but not γ-tocopherol, into plasma. Liver α-tocopherol secretion is under the control of the α-tocopherol transfer protein (TTP). Therefore, to assess γ-tocopherol bioactivities Ttpa-/-, +/- and +/+ mice were fed for 5 weeks diets containing γ-tocopherol 550 (γ-T550), γ-tocopherol 60 (γ-T60) mg/kg that also contained trace amounts of α-tocopherol, a vitamin E-deficient diet, or a control diet. Plasma and tissues from mice fed γ-T550 diets were found to contain similar γ- and α-tocopherol concentrations despite the high dietary γ-tocopherol content; nervous tissues contained almost no γ-tocopherol. Liver vitamin E metabolites (carboxyethyl hydroxychromans, CEHCs) were also measured. In mice with widely ranging liver α- (from 0.7 to 16 nmol/g) and γ-tocopherol concentrations (0 to 13 nmol/g), hepatic α-CEHC was undetectable, but γ-CEHC concentrations (0.1 to 0.8 nmol/g) were correlated with both α- and γ-tocopherol concentrations (P < 0.004). Hepatic cytochrome P450s (CYPs) involved in vitamin E metabolism, Cyp4f and Cyp3a, were also measured. There were no variations in Cyp4f protein expression as related to diet or mouse genotype. However, Cyp3a was correlated (P < 0.0001) with liver α-, but not γ-tocopherol concentrations. These data support the hypothesis that α-tocopherol modulates xenobiotic metabolism by increasing Cyp3a expression, γ-CEHC formation, and the excretion of both γ-tocopherol and γ-CEHC.
UR - http://www.scopus.com/inward/record.url?scp=13844255025&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13844255025&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2004.11.027
DO - 10.1016/j.freeradbiomed.2004.11.027
M3 - Article
C2 - 15721988
AN - SCOPUS:13844255025
VL - 38
SP - 773
EP - 785
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 6
ER -