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Yasukazu Yoshida, Mototada Shichiri, Yoko Akazawa, Aya Umeno, Kazutosh ...
Article type: Article
2014 Volume 88 Issue 2 Pages
63-71
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
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Vitamin E is a generic term for all tocopherol and tocotrienol derivatives. The most abundant and active form of vitamin E isoforms in vivo is α-tocopherol, but recently the roles of other forms of vitamin E have received renewed attention. In this review, we summarize the differences among α-, β-, γ-, δ-tocopherols and tocotrienols specifically regarding the following points; (1) their radical-scavenging efficacies in solution, (2) their physical effects at the liposomal membrane interior and in cells, and (3) their protective effects against cell toxicity and diseases by using animal models. Moreover, the physiological significance and future prospects for using vitamin E, especially tocotrienols, for the prevention and treatment of diseases, especially neurodegenerative diseases, are discussed.
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Akimori Wada
Article type: Article
2014 Volume 88 Issue 2 Pages
72-81
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
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Marked developments in vitamin A research over the past decade have advanced our understanding of the fundamental roles of this vitamin and its physiological significance in living cells. The present research was focused on using retinoid analogs to investigate the function of vitamin A. To reveal the conformation of chromophores in retinal proteins, various retinal analogs were synthesized, and their interaction with an apoprotein was investigated. The circular dichroism spectra of a novel rhodopsin analog consisting of a 11-cis-8,18-alkanoretinal and bovine opsin showed that the torsional angle around the C6-C7 single bond of the retinal in bovine rhodopsin was remarkably similar to that of 8,18-propanoretinal. Comparisons of the interactions of several all-trans-8,16-ethanoretinals and all-trans-8,18-ethanoretinal with the apoprotein in phoborhodopsin revealed that the retinal was incorporated into the protein as the 6s-trans conformation. Furthermore, the fine structure of the ultraviolet/visible absorption spectrum in native phoborhodopsin was found to be affected by the co-planarity of the conjugated polyene structure of the chromophore. Next, through stereoselective synthesis of retinoid isomers, 11-cis-retinal was successfully synthesized using the tricarbonyliron complex. The same methodology was applied to synthesize various 9-substituted 11-cis-retinals to investigate their interactions with bovine opsin. Subsequently, all-trans- and 9-cis-retinoic acids, which are ligands of retinoic acid receptors (all-trans-isomer) and retinoid X receptors (9-cis-isomer), were synthesized from enol triflate and trienyl- or tetraenyl-stannylester in a cesium fluoride-promoted Stille coupling reaction. Using this method, various 9-cis-retinoic acid analogs were also synthesized by replacing the trimethylcyclohexene ring with a cyclic terpenoid moiety and their biological activity was assessed.
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 2 Pages
82-
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
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Susumu Hama, Kenji Fukuzawa, Kentaro Kogure
Article type: Article
2014 Volume 88 Issue 2 Pages
83-91
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
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α-Tocopheryl succinate (TS) has attracted attention as a unique anti-cancer drug for its ability to induce apoptosis in various cancer cells. Furthermore, TS itself readily forms nanovesicles (TS-NVs) and is a prospective tool for use as an antitumor drug delivery system. Activation of various signal transduction factors is also a well-known function of TS. In particular, protein kinase C (PKC), which acts in upstream in the signal transduction, is thought to play an important role in the effects of TS. Our theoretical computational study indicates that TS activates PKC by direct interaction with PKC due to its high structural flexibility. However, TS-NVs are unstable for encapsulating drugs and passive targeting delivery to tumor tissues via an enhanced permeation and retention (EPR) effect. Therefore, to improve the stability of vesicles, we developed a novel nanovesicle consisting of TS and egg phosphatidylcholine (TS-EPC-NVs). The in vivo antitumor activity of TS-EPC-NVs was more potent than that of TS-NVs. Moreover, the in vitro anticancer efficiency of TS-EPC-NVs increased seven-fold. In addition, TS-EPC-NVs encapsulating siRNA showed significant knockdown efficiency. In conclusion, TS-EPC-NVs represent a novel and attractive drug delivery system carrier. It is expected that the drug delivery system shows synergistic anti-tumor activity of the encapsulated drug and the carrier itself.
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Tadanori Hamano, Norimichi Shirafuji, Masaru Kuriyama, Yasunari Nakamo ...
Article type: Article
2014 Volume 88 Issue 2 Pages
92-96
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
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Recently, with the increase of aged people in Japan, the number of people with dementia has been markedly increasing. It was estimated that the number of people with dementia is 4.62 million people in Japan. The most important causes of dementia are Alzheimer's disease (AD), dementia with lewy bodies (DLB), vascular dementia (VD), and frontotemporal dementia (FTD). As treatable dementia, vitamin deficiencies, including vitamin B_1 and B_<12>, and folate deficiencies are important causes. Vitamin B_<12> and folate work as a cofactor of the conversion of homocysteine (Hcy) to methionine. Thus, vitamin B_<12> and folate deficiencies can be the causes of hyperhomocysteinemia. It was reported that hyperhomocysteinemia is an independent risk factor of dementia, including AD (Seshadri et al., 2012). The pathological hallmarks of AD are neurofibrillary tangles (NFT) and senile plaques. The main component of NFT is highly phosphorylated tau protein. We have examined the effect of Hcy on tau metabolism using an inducible model of tauopathy (M1C cells), which express wild type tau protein (4R0N) via tetracycline Off (Tet-Off) induction and neuronal culture (Hamano et al., Neurobiol Aging 2012). Western blot analysis revealed that the administration of L-Hcy increased total tau and phosphorylated tau protein levels. An increase in tau species with C-terminal truncation by caspase 3 was also noted. Activation of caspase 3 was also observed. In a clinical study, folate and vitamin B_<12> levels, as well as Hcy levels, were examined in all patients of the dementia outpatient clinic of University of Fukui. The patients with folate or vitamin B12 deficiency showed hyperhomocysteinemia. After folate supplementation, plasma Hcy levels returned to normal levels. Cognitive functions also improved. Vitamin B_<12> or folate supplementation therapy may prevent the progression of AD pathology in the brain via Hcy reduction.
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Misato Maeda, Hitoshi Shirakawa, Michio Komai
Article type: Article
2014 Volume 88 Issue 2 Pages
97-98
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
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Yoshiki Koriyama, Seiichi Matsugo
Article type: Article
2014 Volume 88 Issue 2 Pages
99-101
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 2 Pages
102-105
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese]
Article type: Article
2014 Volume 88 Issue 2 Pages
106-
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
Article type: Article
2014 Volume 88 Issue 2 Pages
106-107
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese]
Article type: Article
2014 Volume 88 Issue 2 Pages
107-108
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
Article type: Article
2014 Volume 88 Issue 2 Pages
108-109
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
Article type: Article
2014 Volume 88 Issue 2 Pages
109-110
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
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[in Japanese], [in Japanese], [in Japanese], Iffat Ara Sonia Rahman, [ ...
Article type: Article
2014 Volume 88 Issue 2 Pages
110-
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 2 Pages
110-111
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese]
Article type: Article
2014 Volume 88 Issue 2 Pages
112-
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 2 Pages
113-
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
Article type: Article
2014 Volume 88 Issue 2 Pages
113-114
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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Article type: Bibliography
2014 Volume 88 Issue 2 Pages
115-121
Published: February 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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