title: Age-related changes of vitamin E: α-tocopherol levels in plasma and various tissues of mice and hepatic α-tocopherol transfer protein.
abstract: OBJECTIVE
  Despite numerous studies on the RRR- and all-rac-α-tocopherol isoform of vitamin E (VE) during aging, this relationship has not been examined in specific tissues. Since α-tocopherol is the most abundant of VE's eight isoforms, and VE is an important antioxidant that impacts the aging process, we analyzed α-tocopherol levels in plasma and tissues of mice at progressive ages. Moreover, we examined protein and mRNA expression levels of hepatic α-tocopherol transfer protein (α-TTP), which specifically binds α-tocopherol, during aging.
  
  
  METHODS
  The α-tocopherol levels in plasma, liver, cerebrum, hippocampus, cerebellum, heart, kidney, epididymal adipose tissue, testis, pancreas, soleus muscle, plantaris muscle, and duodenum from male C57BL/6NCr mice at 3, 6, 12, 18, and 24 months of age were determined by HPLC and fluorescence detection. Also, hepatic α-TTP protein and mRNA expression levels were analyzed by Western blot and qPCR, respectively.
  
  
  RESULTS
  Tissue-specific, age-related changes of α-tocopherol levels normalized by tissue weight were observed in the liver, cerebrum, hippocampus, cerebellum, heart, kidney, and epididymal adipose tissue. Specifically, α-tocopherol levels in epididymal adipose tissue increased greatly as mice aged from 6 to 24 months. Although hepatic α-TTP protein levels also showed age-related changes, α-TTP mRNA expression levels measured after overnight fasting were not altered.
  
  
  CONCLUSIONS
  In this study, we determined that α-tocopherol levels and hepatic α-TTP protein levels of mice undergo significant tissue-specific, age-related changes. This is the first report to investigate VE in terms of the α-tocopherol levels in plasma and various tissues of mice and hepatic α-TTP protein levels during aging.
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology (TMIG), 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.|Department of Geriatrics and Vascular Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology (TMIG), 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Takisawa
authors.affiliation: Department of Geriatrics and Vascular Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shimokado
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology (TMIG), 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. ishigami@tmig.or.jp.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001835:Body Weight; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D000072470:Cytochrome P450 Family 4 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood*; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000097:blood*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000975:Antioxidants; D002352:Carrier Proteins; D000072470:Cytochrome P450 Family 4; D012333:RNA, Messenger; D014280:Triglycerides; D014810:Vitamin E; D024502:alpha-Tocopherol; C577833:Abca1 protein, mouse; C017763:alpha-tocopherol transfer protein; C465342:Cyp4f14 protein, mouse
keywords: Aging; Liver; Vitamin E; α-Tocopherol; α-Tocopherol transfer protein