Location of α-tocopherol and α-tocotrienol to heterogeneous cell membranes and inhibition of production of peroxidized cholesterol in mouse fibroblasts

Toshiyuki Nakamura, Ayako Noma, Junji Terao

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: α-Tocopherol (α-T) and α-tocotrienol (α-T3) are well recognized as lipophilic antioxidants. Nevertheless, there is limited knowledge on their location in heterogeneous cell membranes. We first investigated the distribution of α-T and α-T3 to the cholesterol-rich microdomains (lipid rafts and caveolae) of heterogeneous cell membranes by incubating these antioxidants with cultured mouse fibroblasts. Findings: Levels of cellular uptake for α-T and α-T3 were adjusted to the same order, as that of the latter was much more efficient than that of the former in the cultured cells. After ultracentrifugation, α-T and α-T3 were partitioned to the microdomain fractions. When the distribution of α-T and α-T3 was further confirmed by using methyl-β-cyclodextrin (which removes cholesterol from membranes), α-T was suggested to be distributed to the microdomains (approx. 9% of the total uptake). The same treatment did not affect α-T3 content in the microdomain fractions, indicating that α-T3 is not located in these cholesterol-rich domains. However, α-T and α-T3 significantly inhibited the production of peroxidized cholesterol when cells were exposed to ultraviolet-A light. Conclusions: These results suggest that α-T and α-T3 can act as membranous antioxidants against photo-irradiated cholesterol peroxidation irrespective of their distribution to cholesterol-rich microdomains.

Original languageEnglish
Article number550
JournalSpringerPlus
Volume3
Issue number1
DOIs
Publication statusPublished - Dec 30 2014
Externally publishedYes

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tocotrienols
tocopherols
fibroblasts
cell membranes
cholesterol
mice
antioxidants
uptake mechanisms
cyclodextrins
ultracentrifugation
peroxidation
cultured cells
ultraviolet radiation
lipids

Keywords

  • Cholesterol hydroperoxide
  • Lipid rafts
  • Microdomains
  • Ultraviolet (UV)-A irradiation
  • α-Tocopherol
  • α-Tocotrienol

ASJC Scopus subject areas

  • General

Cite this

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title = "Location of α-tocopherol and α-tocotrienol to heterogeneous cell membranes and inhibition of production of peroxidized cholesterol in mouse fibroblasts",
abstract = "Background: α-Tocopherol (α-T) and α-tocotrienol (α-T3) are well recognized as lipophilic antioxidants. Nevertheless, there is limited knowledge on their location in heterogeneous cell membranes. We first investigated the distribution of α-T and α-T3 to the cholesterol-rich microdomains (lipid rafts and caveolae) of heterogeneous cell membranes by incubating these antioxidants with cultured mouse fibroblasts. Findings: Levels of cellular uptake for α-T and α-T3 were adjusted to the same order, as that of the latter was much more efficient than that of the former in the cultured cells. After ultracentrifugation, α-T and α-T3 were partitioned to the microdomain fractions. When the distribution of α-T and α-T3 was further confirmed by using methyl-β-cyclodextrin (which removes cholesterol from membranes), α-T was suggested to be distributed to the microdomains (approx. 9{\%} of the total uptake). The same treatment did not affect α-T3 content in the microdomain fractions, indicating that α-T3 is not located in these cholesterol-rich domains. However, α-T and α-T3 significantly inhibited the production of peroxidized cholesterol when cells were exposed to ultraviolet-A light. Conclusions: These results suggest that α-T and α-T3 can act as membranous antioxidants against photo-irradiated cholesterol peroxidation irrespective of their distribution to cholesterol-rich microdomains.",
keywords = "Cholesterol hydroperoxide, Lipid rafts, Microdomains, Ultraviolet (UV)-A irradiation, α-Tocopherol, α-Tocotrienol",
author = "Toshiyuki Nakamura and Ayako Noma and Junji Terao",
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T1 - Location of α-tocopherol and α-tocotrienol to heterogeneous cell membranes and inhibition of production of peroxidized cholesterol in mouse fibroblasts

AU - Nakamura, Toshiyuki

AU - Noma, Ayako

AU - Terao, Junji

PY - 2014/12/30

Y1 - 2014/12/30

N2 - Background: α-Tocopherol (α-T) and α-tocotrienol (α-T3) are well recognized as lipophilic antioxidants. Nevertheless, there is limited knowledge on their location in heterogeneous cell membranes. We first investigated the distribution of α-T and α-T3 to the cholesterol-rich microdomains (lipid rafts and caveolae) of heterogeneous cell membranes by incubating these antioxidants with cultured mouse fibroblasts. Findings: Levels of cellular uptake for α-T and α-T3 were adjusted to the same order, as that of the latter was much more efficient than that of the former in the cultured cells. After ultracentrifugation, α-T and α-T3 were partitioned to the microdomain fractions. When the distribution of α-T and α-T3 was further confirmed by using methyl-β-cyclodextrin (which removes cholesterol from membranes), α-T was suggested to be distributed to the microdomains (approx. 9% of the total uptake). The same treatment did not affect α-T3 content in the microdomain fractions, indicating that α-T3 is not located in these cholesterol-rich domains. However, α-T and α-T3 significantly inhibited the production of peroxidized cholesterol when cells were exposed to ultraviolet-A light. Conclusions: These results suggest that α-T and α-T3 can act as membranous antioxidants against photo-irradiated cholesterol peroxidation irrespective of their distribution to cholesterol-rich microdomains.

AB - Background: α-Tocopherol (α-T) and α-tocotrienol (α-T3) are well recognized as lipophilic antioxidants. Nevertheless, there is limited knowledge on their location in heterogeneous cell membranes. We first investigated the distribution of α-T and α-T3 to the cholesterol-rich microdomains (lipid rafts and caveolae) of heterogeneous cell membranes by incubating these antioxidants with cultured mouse fibroblasts. Findings: Levels of cellular uptake for α-T and α-T3 were adjusted to the same order, as that of the latter was much more efficient than that of the former in the cultured cells. After ultracentrifugation, α-T and α-T3 were partitioned to the microdomain fractions. When the distribution of α-T and α-T3 was further confirmed by using methyl-β-cyclodextrin (which removes cholesterol from membranes), α-T was suggested to be distributed to the microdomains (approx. 9% of the total uptake). The same treatment did not affect α-T3 content in the microdomain fractions, indicating that α-T3 is not located in these cholesterol-rich domains. However, α-T and α-T3 significantly inhibited the production of peroxidized cholesterol when cells were exposed to ultraviolet-A light. Conclusions: These results suggest that α-T and α-T3 can act as membranous antioxidants against photo-irradiated cholesterol peroxidation irrespective of their distribution to cholesterol-rich microdomains.

KW - Cholesterol hydroperoxide

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