![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
-Tocotrienol Antioxidant Action and Cell Signalling1
Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720-3200
2To whom correspondence should be addressed. E-mail: packer{at}socrates.berkeley.edu.
 |
ABSTRACT |
|---|
 TOP ABSTRACT Vitamin E isoforms and...Antioxidant activity of...Absorption and distribution in...Inhibition of cholesterol...Evidence for molecular and...REFERENCES |
|---|
KEY WORDS: • tocotrienols • tocopherols • antioxidants • cell signaling
|
Vitamin E isoforms and their natural sources. |
|---|
|
TOPABSTRACTVitamin E isoforms and...Antioxidant activity of...Absorption and distribution in...Inhibition of cholesterol...Evidence for molecular and...REFERENCES |
|---|
-,
ß-, 
- and 
-tocopherols and -, ß-, - and
-tocotrienols. Tocotrienols differ from the corresponding
tocopherols only in their aliphatic tail. Tocopherols have a phytyl
side chain attached to their chromanol nucleus, whereas the tail of
tocotrienols is unsaturated and forms an isoprenoid chain (Fig. 1
). The various isoforms of tocotrienols differ in their methyl
substituents on the chromanol nucleus. The -form contains 3 methyl
groups, whereas the ß- and - have two and the -form only one
methyl group. Each of these forms of vitamin E has a reportedly
different biopotency (Azzi and Stocker 2000
,
Brigelius-Flohe and Traber 1999
, Traber and Packer 1995
). Humans absorb all forms of vitamin E, but the
body maintains only -tocopherol; this is the basis of the new
recommended dietary allowances of vitamin E, which define the human
requirement only for -tocopherol (International Institute of Medicine 2000
).
|
). Tocotrienols are found in high concentrations in palm oil and rice
bran (Theriault et al. 1999
). Other natural sources
include coconut oil, cocoa butter, soybeans, barley and wheat germ.
Moreover, tocotrienols were also detected in meat and eggs. Sunflower,
peanut, walnut, sesame and olive oils, however contain only tocopherols
(Heinonen and Piironen 1991
).
|
|
Antioxidant activity of tocotrienols. |
|---|
|
TOPABSTRACTVitamin E isoforms and...Antioxidant activity of...Absorption and distribution in...Inhibition of cholesterol...Evidence for molecular and...REFERENCES |
|---|
-tocopherol and -tocotrienol was found in hexane, the
activity of -tocotrienol in scavenging peroxyl radicals is 1.5-fold
higher in liposomes compared with -tocopherol (Serbinova et al. 1991
). In rat liver microsomes, the efficacy of
-tocotrienol to protect against Fe(II)+ NADPH-induced lipid
peroxidation was 40 times higher than that of -tocopherol.
-Tocotrienol also was 6.5 times more effective in the protection of
cytochrome P-450 against oxidative damage. Several reasons have been
suggested for the increased antioxidant activity of -tocotrienol vs.
-tocopherol, focusing on the differences in the tail structure. The
chromanoxyl radical of -tocotrienol (-tocotrienoxyl) has been
found to be recycled in membranes and lipoproteins more quickly than
the corresponding -tocopheroxyl radical (Serbinova et al. 1991
). Nuclear magnetic resonance studies have indicated that
-tocotrienol is located closer to the membrane surface, which may
facilitate recycling. Furthermore, -tocotrienol has a stronger
disordering effect on membranes than -tocopherol and is distributed
more uniformly within the membrane. These properties likely enhance the
interaction of chromanols with lipid radicals (Serbinova et al. 1991
, Suzuki et al. 1993
). As summarized in
Table 2
, there is substantial evidence that tocotrienols may be more efficient
radical scavengers in biomembranes that the corresponding tocopherols.
|
), which has been termed the
"antioxidant network" (Fig. 2
). It is hypothesized that vitamin E acts catalytically, i.e., it is
efficiently reduced from its free radical (chromanoxyl) form, which
arises after quenching lipid radicals, to return back to its reduced
native state. This catalysis occurs through the interactions between
water- and lipid-soluble substances by both nonenzymatic and
enzymatic mechanisms that regenerate vitamin E from its tocotrienoxyl
or tocopheroxyl radical back to tocotrienol and tocopherol,
respectively. Vitamin C can regenerate vitamin E directly, and thiol
antioxidants, such as glutathione and lipoic acid, can regenerate
vitamin E indirectly via vitamin C. Under conditions in which these
systems act synergistically to keep the steady-state concentration
of vitamin E radicals low, the loss or consumption of vitamin E is
prevented. Such recycling effects can be seen in human LDL
(Kagan et al. 1992
) and in membranes enriched with
tocopherols or tocotrienols or by feeding animals vitamin E–enriched
diets (Suarna et al. 1993
, Verlangieri and Bush 1992
).
|
|
Absorption and distribution in tissues. |
|---|
|
TOPABSTRACTVitamin E isoforms and...Antioxidant activity of...Absorption and distribution in...Inhibition of cholesterol...Evidence for molecular and...REFERENCES |
|---|
-tocopherol. In hamsters fed a
mixture of vitamin E isoforms also containing tocotrienols,
-tocopherol was absorbed preferentially. However, tocotrienols could
still be detected in the postprandial plasma of humans, and
tocotrienols were found in all classes of lipoproteins (Hayes et al. 1993
). The liver contains a transfer protein that
preferentially enriches VLDL with -tocopherol (Arita et al. 1995
). Therefore, -tocopherol is secreted preferentially by
the liver in a manner that discriminates between tocopherols and
tocotrienols. Interestingly, the -tocopherol transfer protein
(-TTP)3
was identified as a product of the causative gene for familial isolated
vitamin E deficiency (Ouahchi et al. 1995
). The mRNA of
-TTP was recently detected at low levels in other tissues including
brain, spleen, lung and kidney (Hosomi et al. 1998
). The
presence of a transfer protein that preferentially selects
-tocopherol seems to explain why all other forms of vitamin E have a
lower biological activity in the gestation-resorption assay
compared with -tocopherol. Even though tocotrienols have a higher
radical-scavenging activity than tocopherols, they are less
bioavailable after oral ingestion. It can be hypothesized that if
similar tissue levels could be achieved, tocotrienols would be more
effective antioxidants than tocopherols. There is some evidence
supporting this hypothesis. When supplementation was carried out in a
way that allowed comparable tissue concentrations of -tocopherol and
-tocotrienol to be reached in rat microsomes and mitochondria,
tocotrienol-supplemented heart tissues were more resistant to lipid
peroxidation in vitro than the tocopherol-supplemented counterparts
(Serbinova and Packer 1994
). However, it is important to
note that tocotrienols belong to a family of plant phenolic compounds,
which have a brief and transient nature with respect to their
metabolism, i.e., compared with -tocopherol, they are inferior with
regard to tissue retention and half-life.
The distribution of vitamin E isoforms varies from tissue to tissue. In
mice fed a diet not specifically enriched with tocotrienols, up to 15%
of total vitamin E was composed of tocotrienols; the brain contained no
detectable -tocotrienol levels; in other tissues, 99% of the
vitamin E was present as - or -tocopherol (Podda et al. 1996
). Similarly, in hamsters, tocotrienols were detected in
all tissues except the brain (Hayes et al. 1993
). These
results indicate that tissues may possess the ability to regulate the
vitamin E composition individually. Tocotrienols penetrate rapidly
through skin, and its topical application is an efficient means with
which to enrich skin with vitamin E (Traber et al. 1998
). If skin is exposed to oxidative stress produced by UV or
ozone after the topical application of vitamin E, the increased
antioxidant content is sufficient to combat oxidative stress
(Thiele et al. 1997
, Weber et al. 1997
).
|
Inhibition of cholesterol synthesis. |
|---|
|
TOPABSTRACTVitamin E isoforms and...Antioxidant activity of...Absorption and distribution in...Inhibition of cholesterol...Evidence for molecular and...REFERENCES |
|---|
). In this scenario, tocotrienols
may exert protective effects exceeding those of tocopherols. Cell
culture studies indicate clearly that tocotrienols influence
cholesterol synthesis by directly regulating the expression of
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase),
principally through a postranscriptional process involving accelerated
degradation of the reductase protein (Parker et al. 1993
). In pigs with inherited hyperlipidemia, dietary
tocotrienols from a tocotrienol-rich fraction of palm oil (TRF)
reduced the concentrations of plasma cholesterol and apolipoprotein B,
thromboxane B2 and platelet factor 4, indicating
a protective effect on endothelium and platelet aggregation
(Qureshi et al. 1991a
). When rats were fed an
atherogenic diet, both -tocotrienol and -tocopherol significantly
lowered plasma lipid concentrations (Watkins et al. 1993
). Moreover, supplementation with TRF reduced plasma
cholesterol levels in a human pilot study lasting 8 wk (Qureshi et al. 1991b
). In a trial of 4 wk, these results were
confirmed, and a carry-over effect after the end of supplementation
was reported (Qureshi et al. 1995
). Interestingly,
dietary -tocopherol attenuated the cholesterol-lowering effect
of -tocotrienol in both humans and chickens (Qureshi et al. 1995
and 1996
). In a double-blind, placebo-controlled
trial, no effect of a vitamin E supplement rich in tocotrienols (140
mg/d for 6 wk) on serum lipids, lipoproteins or platelet function in
men with mildly elevated serum lipid concentrations was found
(Mensink et al. 1999
). Furthermore, -tocotrienyl
acetate, which is hydrolyzed, absorbed and detectable in human plasma,
did not lower cholesterol in hypercholesterolemic subjects but was
potent in decreasing LDL oxidizability (O’Byrne et al. 2000
). Some of the conflicting results in the literature
regarding the cholesterol-lowering effects of tocotrienols might be
related to differences in plasma tocotrienol levels. In vitro studies
with HepG2 cells suggest that tocotrienols are effective at levels of
10 µmol/L (Parker et al. 1993
), which may not have
been reached in the human trials summarized above. Moreover, it has
been reported recently that humans do not respond uniformly to the
cholesterol-lowering action of tocotrienols, particularly when
cholesterol and alcohol intakes are not controlled (Qureshi et al. 1997
). |
Evidence for molecular and cell biological aspects of tocopherol and tocotrienol on signal transduction |
|---|
|
TOPABSTRACTVitamin E isoforms and...Antioxidant activity of...Absorption and distribution in...Inhibition of cholesterol...Evidence for molecular and...REFERENCES |
|---|
Tocotrienols belong to a phytochemical class of isoprenoid molecules.
These compounds share a common precursor, mevalonic acid. Tocotrienols
are mixed isoprenoids, meaning that only a part, the lipophilic chain,
is derived via the isoprenoid pathway. Isoprenoids have been shown to
exhibit anticarcinogenic properties. When different vitamin E isoforms
were analyzed, it could be demonstrated that -tocopherol and
-tocotrienol inhibited tumor promotion in Raji-cells most
effectively (Goh et al. 1994
). Tocotrienols from TRF
inhibited the proliferation of human breast cancer cell lines
(Guthrie 1997
, Nesaretnam et al. 1995
).
The inhibition was found to be independent of the estrogen receptor
status of the cell lines (Nesaretnam et al. 1998
).
Isoprenoids, including tocotrienols, also suppressed the growth of
murine B16 melanomas in vitro and in vivo (He et al. 1997
). Interestingly, correlations between the late-stage
tumor-suppressive potency of diverse isoprenoids and their effect of
HMG CoA reductase activity approached unity. It is hypothesized that
vitamin E might exert antiproliferative properties by interfering with
signal transduction events involving protein kinase C (PKC). It is has
been shown that -tocopherol inhibits the proliferation of smooth
muscle cells by inhibition of PKC (Tasinato et al. 1995
). This effect was specific for -tocopherol as opposed
to the isoform ß-tocopherol (Azzi et al. 1993
). There
is no information, however, on the potency of -tocotrienol on PKC
activity, which shares the structure of the chromanol nucleus with
-tocopherol. Recently, it has been reported that isoprenoids,
including tocotrienols, induce cell-cycle arrest in the G-1 phase
and apoptosis in human and murine tumor cells (Yu et al. 1999
). Because these effects can be observed with different
isoprenoids, which are not antioxidants, it is possible that the
anticarcinogenic effects of tocotrienols are not necessarily related to
their antioxidant properties.
Neuroprotection and src activity.
Elevated levels of glutamate have been implicated in a wide range of
neurological diseases, including epilepsy, cerebral ischemia,
Huntington’s disease and Parkinson’s disease. Receptor-mediated
glutamate excitotoxicity is believed to be a major mechanism of damage
in these pathologies, and induction of oxidative stress by glutamate
has been demonstrated to be the primary cytotoxic mechanisms in cell
lines such as C6 glial cells (Han et al. 1997
), PC-12
neuronal cells (Pereira and Oliveira 1997
), immature
cortical neuron cells (Murphy et al. 1990
) and
oligodendroglia cells (Oka et al. 1993
). It has been
demonstrated that high glutamate levels block cystine uptake via amino
acid transporter Xc-, resulting in a significant
depletion of cellular glutathione (GSH). A GSH-depleted state
impairs cellular antioxidant defenses, followed by an increased
vulnerability of the cell to reactive oxygen species (ROS). The
mitochondrial electron transport chain has been shown to be a source of
ROS production during glutamate-induced apoptosis (Tan et al. 1998
). Recently, vitamin E isoforms were tested in a model
of neuronal cell death in which HT4 neuronal cells were challenged with
glutamate (Sen et al. 2000
). Tocotrienols counteracted
glutamate-induced cell death at much lower concentrations than
tocopherols. Moreover, tocotrienols effectively inhibited the
activation of pp60 c-src kinase, a kinase that is centrally
involved in glutamate-induced cell death. It is hypothesized that
these protective effects of tocotrienols are probably independent of
their antioxidant activity because tocopherols were effective only at
multifold higher concentrations (Sen et al. 2000
). The
activity of src kinase has also been shown in the progression of breast
cancer (Muthuswamy and Muller 1995
). Elevated levels of
src kinase have also been found in human skin tumors (Barnekow et al. 1987
). Because of the key involvement of src kinase in
neurodegenerative diseases and oncogenesis, inhibition of these kinases
would seem to be a likely basis for developing a strategy to create
neuroprotective and anticancer drugs.
Tocotrienols make up a considerable portion of total vitamin E in many
food sources. In vitro, they have been shown to exhibit enhanced
antioxidant properties compared with tocopherols. In addition, they
have been shown to have cholesterol-lowering, anticarcinogenic and
neuroprotective properties, which may not be related to their
antioxidant function. After oral ingestion, however, they are not
recognized by the -TTP and thus only have a short half-life,
which accounts for their low bioavailability. A promising approach to
utilize tocotrienols may be the topical application onto the skin. In
this scenario, uptake and distribution within the skin do not depend on
transfer proteins, thereby allowing active concentrations to be reached
in skin after topical supplementation.
|
FOOTNOTES |
|---|
3 Abbreviations: -TTP, -tocopherol transfer
protein; GSH, glutathione; HMG-CoA reductase,
3-hydroxy-3-methylglutaryl-coenzyme A reductase; PKC, protein kinase C;
ROS, reactive oxygen species; TRF, tocotrienol-rich fraction of
palm oil.
|
REFERENCES |
|---|
|
TOPABSTRACTVitamin E isoforms and...Antioxidant activity of...Absorption and distribution in...Inhibition of cholesterol...Evidence for molecular and...REFERENCES |
|---|
1. Arita M., Sato Y., Miyata A., Tanabe T., Takahashi E., Kayden H. J., Arai H., Inoue K. Human alpha-tocopherol transfer protein: cDNA cloning, expression and chromosomal localization. Biochem. J. 1995;306:437-443
2.
Azzi A., Boscoboinik D., Chatelain E., Ozer N. K., Stäuble B. d--Tocopherol control of cell proliferation. Mol. Asp. Med. 1993;14:265-271
3. Azzi A., Stocker A. Vitamin E: non-antioxidant roles. Prog. Lipid Res. 2000;39:231-255[Medline]
4.
Barnekow A., Paul E., Schartl M. Expression of the c-src protooncogene in human skin tumors. Cancer Res 1987;47:235-240
5.
Brigelius-Flohé R., Traber M. G. Vitamin E: function and metabolism. FASEB J 1999;13:1145-1155
6.
Constantinescu A., Han D., Packer L. Vitamin E recycling in human erythrocyte membranes. J. Biol. Chem. 1993;268:10906-10913
7. Goh S. H., Hew N. F., Norhanom A. W., Yadav M. Inhibition of tumour promotion by various palm-oil tocotrienols. Int. J. Cancer 1994;57:529-531[Medline]
8. Guthrie N., Gapor A., Chambers A. F., Carroll K. K. Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells by palm oil tocotrienols and tamoxifen, alone and in combination. J. Nutr. 1997;127:544S-548S
9.
Han D., Sen C. K., Roy S., Kobayashi M. S., Tritschler H. J., Packer L. Protection against glutamate-induced cytotoxicity in C6 glial cells by thiol antioxidants. Am. J. Physiol. 1997;273:R1771-R1778
10. Hayes K. C., Pronczuk A., Liang J. S. Differences in the plasma transport and tissue concentrations of tocopherols and tocotrienols: observations in humans and hamsters. Proc. Soc. Exp. Biol. Med. 1993;202:353-359[Abstract]
11.
He L., Mo H., Hadisusilo S., Qureshi A. A., Elson C. E. Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo. J. Nutr. 1997;127:668-674
12. Heinonen M., Piironen V. The tocotrienol, and vitamin-E content of the average Finnish diet. Int. J. Vitam. Nutr. Res. 1991;61:27-32[Medline]
13. Hosomi A., Goto K., Kondo H., Iwatsubo T., Yokota T., Ogawa M., Arita M., Aoki J., Arai H., Inoue K. Localization of alpha-tocopherol transfer protein in rat brain. Neurosci. Lett. 1998;256:159-162[Medline]
14. International Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference Intake of Vitamin C, Vitamin E, Selenium, and Carotonoids 2000:58-72 National Academy Press Washington, DC.
15. Kagan V. E., Serbinova E. A., Forte T., Scita G., Packer L. Recycling of vitamin E in human low density lipoproteins. J. Lipid Res. 1992;33:385-397[Abstract]
16.
Mensink R. P., van Houwelingen A. C., Kromhout D., Hornstra G. A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. Am. J. Clin. Nutr. 1999;69:213-219
17. Meydani M. Vitamin E. Lancet 1995;345:170-175[Medline]
18. Murphy T. H., Schnaar R. L., Coyle J. T. Immature cortical neurons are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake. FASEB J 1990;4:1624-1633[Abstract]
19. Muthuswamy S. K., Muller W. J. Activation of Src family kinases in Neu-induced mammary tumors correlates with their association with distinct sets of tyrosine phosphorylated proteins in vivo. Oncogene 1995;11:1801-1810[Medline]
20. Nesaretnam K., Guthrie N., Chambers A. F., Carroll K. K. Effect of tocotrienols on the growth of a human breast cancer cell line in culture. Lipids 1995;30:1139-1143[Medline]
21. Nesaretnam K., Stephen R., Dils R., Darbre P. Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status. Lipids 1998;33:461-469[Medline]
22. O’Byrne D. O., Grundy S., Packer L., Devaraj S., Baldenius K., Hoppe P., Krämer K., Jialal I., Traber M. G. Studies of LDL oxidation following alpha-, gamma- or delta-tocotrienyl acetate supplementation of hypercholesterolemic humans. Free Radic. Biol. Med. 2000;29:834-845[Medline]
23. Oka A., Belliveau M. J., Rosenberg P. A., Volpe J. J. Vulnerability of oligodendroglia to glutamate—pharmacology, mechanisms, and prevention. J. Neurosci. 1993;13:1441-1453[Abstract]
24. Ong A.S.H. Natural sources of tocotrienols. Packer L. Fuchs J. eds. Vitamin E in Health and Disease 1993:3-8 Marcel Dekker, Inc New York, NY.
25. Ouahchi K., Arita M., Kayden H., Hentati F., Ben Hamida M., Sokol R., Arai H., Inoue K., Mandel J. L., Koenig M. Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein. Nat. Genet. 1995;9:141-145[Medline]
26.
Parker R. A., Pearce B. C., Clark R. W., Gordon D. A., Wright J. J. Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J. Biol. Chem. 1993;268:11230-11238
27. Pereira C. M., Oliveira C. R. Glutamate toxicity on a PC12 cell line involves glutathione (GSH) depletion and oxidative stress. Free Radic. Biol. Med. 1997;23:637-647[Medline]
28. Podda M., Weber C., Traber M. G., Packer L. Simultaneous determination of tissue tocopherols, tocotrienols, ubiquinols, and ubiquinones. J. Lipid Res. 1996;37:893-901[Abstract]
29. Qureshi A. A., Bradlow B. A., Brace L., Manganello J., Peterson D. M., Pearce B. C., Wright J. J., Gapor A., Elson C. E. Response of hypercholesterolemic subjects to administration of tocotrienols. Lipids 1995;30:1171-1177[Medline]
30. Qureshi A. A., Bradlow B. A., Salser W. A., Brace L. D. Novel tocotrienols of rice bran modulate cardiovascular disease risk parameters of hypercholesterolemic humans. J. Nutr. Biochem. 1997;8:290-298
31.
Qureshi A. A., Pearce B. C., Nor R. M., Gapor A., Peterson D. M., Elson C. E. Dietary -tocopherol attenuates the impact of -tocotrienol on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in chickens. J. Nutr. 1996;126:389-394
32.
Qureshi A. A., Qureshi N., Hasler-Rapacz J. O., Weber F. E., Chaudhary V., Crenshaw T. D., Gapor A., Ong A. S., Chong Y. H., Peterson D., Rapacz J. Dietary tocotrienols reduce concentrations of plasma cholesterol, apolipoprotein B, thromboxane B2, and platelet factor 4 in pigs with inherited hyperlipidemias. Am. J. Clin. Nutr. 1991a;53:1042S-1046S
33.
Qureshi A. A., Qureshi N., Wright J. J., Shen Z., Kramer G., Gapor A., Chong Y. H., DeWitt G., Ong A., Peterson D. M., Bradlow B. A. Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee). Am. J. Clin. Nutr. 1991b;53:1021S-1026S
34.
Sen C. K., Khanna S., Roy S., Packer L. Molecular basis of vitamin E action. Tocotrienols potently inhibit glutamate-induced pp60c-scr kinase activation of HT4 neuronal cells. J. Biol. Chem 2000;275:13049-13055
35. Serbinova E., Kagan V., Han D., Packer L. Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol. Free Radic. Biol. Med. 1991;10:263-275[Medline]
36. Serbinonva E. A., Packer L. Antioxidant properties of tocopherol and tocotrienol. Methods Enzymol 1994;234:354-367[Medline]
37. Sheppard A. J., Pennington J.A.T., Weihrauch J. L. Analysis and distribution of vitamin E in vegetable oils and foods. Packer L. Fuchs J. eds. Vitamin E in Health and Disease 1993:9-31 Marcel Dekker, Inc New York, NY.
38. Suarna C., Hood R. L., Dean R. T., Stocker R. Comparative antioxidant activity of tocotrienols and other natural lipid-soluble antioxidants in a homogeneous system, and in rat and human lipoproteins. Biochim. Biophys. Acta 1993;1166:163-170[Medline]
39. Suzuki Y. J., Tsuchiya M., Wassall S. R., Choo Y. M., Govil G., Kagan V. E., Packer L. Structural and dynamic membrane properties of alpha-tocopherol and alpha-tocotrienol: implication to the molecular mechanism of their antioxidant potency. Biochemistry 1993;32:10692-10699[Medline]
40.
Tan S. L., Sagara Y., Lin Y. B., Maher P., Schubert D. The regulation of reactive oxygen species production during programmed cell death. J. Cell Biol. 1998;141:1423-1432
41.
Tasinato A., Boscoboinik D., Bartoli G. M., Maroni P., Azzi A. d--Tocopherol inhibition of vascular smooth muscle cell proliferation occurs at physiological concentrations, correlates with protein kinase C inhibition, and is independent of its antioxidant properties. Proc. Natl. Acad. Sci. U.S.A. 1995;92:12190-12194
42. Theriault A., Chao J. T., Wang Q., Gapor A., Adeli K. Tocotrienol: a review of its therapeutic potential. Clin. Biochem. 1999;32:309-319[Medline]
43. Thiele J. J., Traber M. G., Podda M., Tsang K., Cross C. E., Packer L. Ozone depletes tocopherols and tocotrienols topically applied to murine skin. FEBS Lett 1997;401:167-170[Medline]
44.
Traber M. G., Packer L. Vitamin E—beyond antioxidant function. Am. J. Clin. Nutr. 1995;62:S1501-S1509
45.
Traber M. G., Rallis M., Podda M., Weber C., Maibach H. I., Packer L. Penetration and distribution of -tocopherol, - or -tocotrienols applied individually onto murine skin. Lipids 1998;33:87-91[Medline]
46.
Verlangieri A. J., Bush M. J. Effects of d--tocopherol supplementation on experimentally induced primate atherosclerosis. J. Am. Coll. Nutr. 1992;11:131-138[Abstract]
47.
Watkins T., Lenz P., Gapor A., Struck M., Tomeo A., Bierenbaum M. -Tocotrienol as a hypocholesterolemic and antioxidant agent in rats fed atherogenic diets. Lipids 1993;28:1113-1118[Medline]
48. Weber C., Podda M., Rallis M., Thiele J. J., Traber M. G., Packer L. Efficacy of topically applied tocopherols and tocotrienols in protection of murine skin from oxidative damage induced by UV-irradiation. Free Radic. Biol. Med. 1997;22:761-769[Medline]
49. Yu W., Simmons-Menchaca M., Gapor A., Sanders B. G., Kline K. Induction of apoptosis in human breast cancer cells by tocopherols and tocotrienols. Nutr. Cancer 1999;33:26-32[Medline]
This article has been cited by other articles:
|
|
 |
|
  C. Abe, S. Ikeda, T. Uchida, K. Yamashita, and T. Ichikawa Triton WR1339, an Inhibitor of Lipoprotein Lipase, Decreases Vitamin E Concentration in Some Tissues of Rats by Inhibiting Its Transport to Liver J. Nutr., February 1, 2007; 137(2): 345 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tanito, Y. Yoshida, S. Kaidzu, Z.-H. Chen, O. Cynshi, K.-i. Jishage, E. Niki, and A. Ohira Acceleration of Age-Related Changes in the Retina in {alpha}-Tocopherol Transfer Protein Null Mice Fed a Vitamin E-Deficient Diet Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 396 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fairus, R. M Nor, H. M Cheng, and K. Sundram Postprandial metabolic fate of tocotrienol-rich vitamin E differs significantly from that of {alpha}-tocopherol. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 835 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yi and N. Maeda Endogenous Production of Lipoic Acid Is Essential for Mouse Development Mol. Cell. Biol., September 15, 2005; 25(18): 8387 - 8392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. SAITO, Y. YOSHIDA, K. NISHIO, M. HAYAKAWA, and E. NIKI Characterization of Cellular Uptake and Distribution of Vitamin E Ann. N.Y. Acad. Sci., December 1, 2004; 1031(1): 368 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-A. Gomez, X. Molero, E. Vaquero, A. Alonso, A. Salas, and J.-R. Malagelada Vitamin E attenuates biochemical and morphological features associated with development of chronic pancreatitis Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G162 - G169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Svilaas, A. K. Sakhi, L. F. Andersen, T. Svilaas, E. C. Strom, D. R. Jacobs Jr., L. Ose, and R. Blomhoff Intakes of Antioxidants in Coffee, Wine, and Vegetables Are Correlated with Plasma Carotenoids in Humans J. Nutr., March 1, 2004; 134(3): 562 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Rippert, C. Scimemi, M. Dubald, and M. Matringe Engineering Plant Shikimate Pathway for Production of Tocotrienol and Improving Herbicide Resistance Plant Physiology, January 1, 2004; 134(1): 92 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Saito, Y. Yoshida, T. Akazawa, K. Takahashi, and E. Niki Cell Death Caused by Selenium Deficiency and Protective Effect of Antioxidants J. Biol. Chem., October 10, 2003; 278(41): 39428 - 39434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ikeda, T. Tohyama, H. Yoshimura, K. Hamamura, K. Abe, and K. Yamashita Dietary {alpha}-Tocopherol Decreases {alpha}-Tocotrienol but Not {gamma}-Tocotrienol Concentration in Rats J. Nutr., February 1, 2003; 133(2): 428 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Halvorsen, K. Holte, M. C. W. Myhrstad, I. Barikmo, E. Hvattum, S. F. Remberg, A.-B. Wold, K. Haffner, H. Baugerod, L. F. Andersen, et al. A Systematic Screening of Total Antioxidants in Dietary Plants J. Nutr., March 1, 2002; 132(3): 461 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. RICCIARELLI, J.-M. ZINGG, and A. AZZI Vitamin E: protective role of a Janus molecule FASEB J, November 1, 2001; 15(13): 2314 - 2325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ikeda, K. Toyoshima, and K. Yamashita Dietary Sesame Seeds Elevate {alpha}- and {gamma}-Tocotrienol Concentrations in Skin and Adipose Tissue of Rats Fed the Tocotrienol-Rich Fraction Extracted from Palm Oil J. Nutr., November 1, 2001; 131(11): 2892 - 2897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Qureshi, W. A. Salser, R. Parmar, and E. E. Emeson Novel Tocotrienols of Rice Bran Inhibit Atherosclerotic Lesions in C57BL/6 ApoE-Deficient Mice J. Nutr., October 1, 2001; 131(10): 2606 - 2618. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
