Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Toward a new era of the Nagoya Journal of Medical Science: message from the new editor-in-chief. Invited

Toyokuni S.

Nagoy J Med Sci Vol. 72 page： 107-109 2010

A beverage containing fermented black soybean ameliorates ferric nitrilotriacetate-induced renal oxidative damage in rats. Reviewed

Okazaki Y, Iqbal M, Kawakami N, Yamamoto Y, Toyokuni S and Okada S.

J Clin Biochem Nutr Vol. 47 page： 198-207 2010

Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials. Reviewed

Nagai H and Toyokuni S.

Arch Biochem Biophys Vol. 502 page： 1-7 2010

Genome-scale approaches to investigate oxidative DNA damage. Reviewed

Akatsuka S and Toyokuni S.

J Clin Biochem Nutr Vol. 47 page： 91-97 2010

Lipid peroxidation generates a body odor component trans-2-nonenal covalently bound to protein in vivo. Reviewed

Ishino K, Wakita C, Shibata T, Toyokuni S, Machida S, Matsuda S, Matsuda T and Uchida K.

J Biol Chem Vol. 285 page： 15302-15313 2010

Suppression of SLC11A2 expression is essential to maintain duodenal integrity during dietary iron overload. Reviewed

Shirase T, Mori K, Okazaki Y, Itoh K, Yamamoto M, Tabuchi M, Kishi F, Jiang L, Akatsuka S, Nakao K and Toyokuni S.

Am J Pathol Vol. 177 page： 677-685 2010

Novel method for efficient collection of normal mesothelial cells in vivo. Reviewed

Jiang L, Yamashita Y and Toyokuni S.

J Clin Biochem Nutr Vol. 46 page： 265-268 2010

Homozygous Deletion of CDKN2A/2B is a Hallmark of Iron-induced High-grade Rat Mesothelioma International journal

Yasumasa Okazaki, Quan Hu, Shinya Akatsuka, Hiroki Ohara, Hirotaka Nagai, Takashi Takahashi, Shinya Toyokuni

FREE RADICAL BIOLOGY AND MEDICINE Vol. 49 page： S67 - S67 2010

Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials. Reviewed

Nagai H, Toyokuni S

Arch Biochem Biophys Vol. 502 page： 1-7 2010

CD8+CD122+ Regulatory T Cells and CD4+ Treg Cooperatively Prevent and Cure CD4+ cell-induced Colitis. Reviewed

Endharti AT, Okuno Y, Shi Z, Misawa N, Toyokuni S, Ito M, Isobe KI, Suzuki H

Vol. 186 page： 41-52 2010

Stage-specific roles of fibulin-5 during oxidative stress-induced renal carcinogenesis in rats. Reviewed

Ohara H, Akatsuka S, Nagai H, Liu YT, Jiang L, Okazaki Y, Yamashita Y, Nakamura T, Toyokuni S

Free Radic Res page： (in press) 2010

Toward a new era of the Nagoya Journal of Medical Science: message from the new editor-in-chief. Invited

Toyokuni S

Nagoy J Med Sci Vol. 72 page： 107-109 2010

脳梗塞モデルラット作成前に実施する運動の効果および作用機序の検討:～抗酸化作用に着目して～

濱川みちる, 石田章真, 玉越敬悟, 嶋田悠, 中島宏樹, 豊國伸哉, 石田和人

東海北陸理学療法学術大会誌 Vol. 26 ( 0 ) page： 35 - 35 2010

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：東海北陸理学療法学術大会

【目的】脳梗塞モデル作成前の運動には、梗塞体積減少、運動機能改善などの脳梗塞の障害軽減効果があると報告されている。また、運動は抗酸化作用を高めることが報告されているが、抗酸化作用が脳梗塞の障害軽減効果にいかに関与するかについては不明である。そこで本研究では、脳梗塞発症前に運動を行うことの効果および作用機序を抗酸化作用に着目して検討する。【方法】実験動物にはWistar系雄性ラット(5週齢)を用いた。無作為に運動群と非運動群に分け、運動群はトレッドミル運動(15 m / min、30分/日)を3週間毎日行った。非運動群は1日30分間走行させずにトレッドミル装置内に暴露させた。介入終了の翌日、各群に脳梗塞モデル作成手術を施行した。手術24時間後に、麻痺の重症度を評価するNeurological Deficits(ND)、歩行時のバランス能力の評価としてBeam Walking(BW)、はしご上の歩行における前肢の協調運動機能を評価するLadder test、前肢の感覚運動機能の評価としてLimb Placing(LP)を行った。その直後に脳を採取し、TTC染色により非梗塞半球体積に対する梗塞体積の割合を算出した。また、酸化ストレス産物の指標として4-hydroxy-2-nonenal (4-HNE)及び8-Hydroxydeoxyguanosine(8-OHdG)の免疫染色を行った。統計学的検定には、対応のないt検定とMann-WhitneyのU検定を用い、有意水準は5％未満とした。【結果】NDとladder testにおいて、運動群が非運動群と比較して有意に障害が軽減した（p < 0.05）。また、他の機能評価や梗塞体積については群間に有意差は認められなかった。免疫染色では、非梗塞側半球で運動群に比べ非運動群は4-HNE陽性細胞が多くみられた。しかし、8-OHdG染色では差を認めなかった。【まとめ】脳梗塞前の運動は、梗塞後の運動機能改善効果をもたらしたものの、梗塞体積は非運動群と同程度であった。しかし、脂質過酸化の指標である4-HNE陽性細胞は非運動群の非梗塞側でより多く見られ、運動による酸化ストレス抑制効果が示された。 本研究は科研費（22500456）の助成を受けたものである。

DOI： 10.11529/thpt.26.0.35.0

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Asbestos-induced Carcinogenesis is Oxidative Stress-dependent

Shinya Toyokuni, Li Jiang, Hirotaka Nagai, Hiroki Ohara, Yasumasa Okazaki, Shinya Akatsuka, Yoriko Yamashita

FREE RADICAL BIOLOGY AND MEDICINE Vol. 49 page： S72 - S72 2010

S1-3 Elucidation of asbestos-induced mesothelial carcinogenesis and its prevention stragegy(Symposium 1: Biomarkers in Environmental Mutagen Research: Lifestyle-related and Environmental Factors)

ToyokuniShinya

( 38 ) page： 75 2009.11

ITPase-deficient mice show growth retardation and die before weaning. Reviewed

Behrmanech M, Sakumi K, Abolhassani N, Toyokuni S, Oka S, Ohnishi YN, Tsuchimoto D, Nakabeppu Y.

Cell Death Differ. Vol. 16 page： 1315-1322 2009.10

Potent antioxidative acticity of Vineatrol® 30 grapevine-shoot extract. Reviewed

Müller C, Ullmann K, Wilkins A, Winterhalter P, Toyokuni S and Steinberg P.

Biosci Biotechnol Biochem Vol. 73 page： 1831-1836 2009.8

Elucidation of Asbestos-induced Carcinogenesis and Its Application to Prevention, Diagnosis and Treatment in Relation to Iron

Toyokuni Shinya

Haigan Vol. 49 ( 4 ) page： 362 - 367 2009.8

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japan Lung Cancer Society

Objective. Respiratory exposure to asbestos has been associated with mesothelioma in humans. However, its carcinogenic mechanism is still unclear. Methods. Here we studied the ability of chrysotile, crocidolite and amosite fibers to induce oxidative DNA damage and the modifying factors using 4 distinct approaches. Results. Electron spin resonance analyses showed that crocidolite and amosite containing high amounts of iron, but not chrysotile, catalyzed hydroxyl radical formation in the presence of hydrogen peroxide, which was enhanced by an iron chelator, nitrilotriacetic acid, and suppressed by Desferal®. Iron chelators, such as citrate, ATP and GTP, did not inhibit this reaction. Second, we used time-lapse videomicroscopy to evaluate how cells deal with asbestos fibers. RAW264.7 cells, MeT-5A and HeLa cells engulfed asbestos fibers, which reached not only cytoplasm but also the nucleus. Third, we utilized supercoiled plasmid DNA to evaluate the ability of each type of asbestos to induce DNA double strand breaks (DSBs). Crocidolite and amosite, but not chrysotile, induced DNA DSBs in the presence of iron chelators. We cloned the fragments to identify break ends. DSBs tended to occur within repeat sequences and between two G: C sequences. Finally, intraperitoneal administration of each type of asbestos to rats induced not only formation of nuclear 8-hydroxy-2'-deoxyguanosine in the mesothelium but also significant iron deposits in the spleen. Conclusion. Together with the established carcinogenicity of intraperitoneal chrysotile, our data suggest that asbestos-associated catalytic iron, whether constitutional or induced by other mechanisms, plays a role in asbestos-induced carcinogenesis and that chemoprevention may be possible through targeting the catalytic iron.

DOI： 10.2482/haigan.49.362

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Potent Antioxidative Activity of Vineatrol (R) 30 Grapevine-shoot Extract Reviewed

Carsten Mueller, Kristina Ullmann, Andrea Wilkens, Peter Winterhalter, Shinya Toyokuni, Pablo Steinberg

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY Vol. 73 ( 8 ) page： 1831 - 1836 2009.8

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

The health promoting effects of a grapevine-shoot extract named Vineatrol (R) 30, which contains resveratrol (Resv) as well as considerable amounts of Resv oligomers, have recently been investigated. In the present study, we analyzed the free radical scavenging capacity, the ability to inhibit lipid peroxidation, and the capacity to enhance the human glutathione peroxidase 1 (GPx) and the human superoxide dismutase 1 (SOD) gene promoter activities of Vineatrol (R) 30. Vineatrol (R) 30 was able to scavenge the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid radical cation and led to concentration-dependent inhibition of lipid peroxidation, Vineatrol (R) 30 not being superior to Resv alone in both cases. Vineatrol (R) 30 also enhanced the gene promoter activities of human GPx and SOD expressed in V79 cells, whereas this effect could not be demonstrated for Resv. In summary, the results presented in this study show that the Vineatrol (R) 30 grapevine-shoot extract is a free radical scavenger and potent antioxidant at non-eytotoxic concentrations.

DOI： 10.1271/bbb.90213

B細胞性芽球型リンパ腫ゲノムにおけるマイクロサテライト不安定性(Microsatellite instability in the genome of B-lymphoblastic lymphoma)

リチャード・カシンスキー, 鶴山竜昭, 河野文彦, 平塚拓也, 尾関宗孝, 豊國伸哉, 日合弘, 玉木敬二

日本癌学会総会記事 Vol. 68回 page： 163 - 163 2009.8

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