研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

分割表示 1,287 件中 621 - 640 件目／全件表示 >>

Potent antioxidative acticity of Vineatrol® 30 grapevine-shoot extract. 査読有り

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

Biosci Biotechnol Biochem 73 巻頁： 1831-1836 2009年8月

Elucidation of asbestos-induced carcinogenesis and its application to prevention, diagnosis and treatment in relation to iron 国際誌 Open Access

Toyokuni S.

Japanese Journal of Lung Cancer 49 巻 ( 4 ) 頁： 362 - 367 2009年8月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Lung Cancer

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. © 2009 The Japan Lung Cancer Society.

DOI： 10.2482/haigan.49.362

Scopus

CiNii Research

researchmap

Potent Antioxidative Activity of Vineatrol®30 Grapevine-shoot Extract 査読有り国際誌 Open Access

Müller, C; Ullmann, K; Wilkens, A; Winterhalter, P; Toyokuni, S; Steinberg, P

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 73 巻 ( 8 ) 頁： 1831 - 1836 2009年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Bioscience, Biotechnology and Biochemistry

The health promoting effects of a grapevine-shoot extract named Vineatrol®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®30. Vineatrol®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®30 not being superior to Resv alone in both cases. Vineatrol®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®30 grapevine-shoot extract is a free radical scavenger and potent antioxidant at non-cytotoxic 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 68回巻頁： 163 - 163 2009年8月

Genetic reconstruction of mouse spermatogonial stem cell self-renewal in vitro by Ras-cyclin D2 activation. 査読有り国際誌 Open Access

Lee J, Kanatsu-Shinohara M, Morimoto H, Kazuki Y, Takashima S, Oshimura M, Toyokuni S, Shinohara T

Cell stem cell 5 巻 ( 1 ) 頁： 76 - 86 2009年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cell Stem Cell

Spermatogonial stem cells (SSCs) undergo self-renewal division and support spermatogenesis. Although several cytokines coordinate to drive SSC self-renewal, little is known about the mechanisms underlying this process. We investigated the molecular mechanism by reconstructing SSC self-renewal in vitro without exogenous cytokines. Activation of Ras or overexpression of cyclins D2 and E1, both of which were induced by Ras, enabled long-term self-renewal of cultured spermatogonia. SSCs with activated Ras responded properly to differentiation signals and underwent spermatogenesis, whereas differentiation was abrogated in cyclin transfectants after spermatogonial transplantation. Both Ras- and cyclin-transfected cells produced seminomatous tumors, suggesting that excessive self-renewing stimulus induces oncogenic transformation. In contrast, cells that overexpressed cyclin D1 or D3 failed to make germ cell colonies after transplantation, which indicated that cyclin expression pattern is an important determinant to long-term SSC recolonization. Thus, the Ras-cyclin D2 pathway regulates the balance between tissue maintenance and tumorigenesis in the SSC population. © 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.stem.2009.04.020

Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenic defects. 査読有り

Takashima S, Takehashi M, Lee J, Chuma S, Okano M, Hata K, Suetake I, Nakatsuji N, Miyoshi H, Tajima S, Tanaka Y, Toyokuni S, Sasaki H, Kanatsu-Shinohara M, Shinohara S.

81 巻頁： 155-164 2009年7月

Genetic reconstruction of mouse spermatogonial stem cell self-renewal in vitro by Ras-cyclin D2 activation. 査読有り

Lee J, Kanatsu-Shinohara M, Morimoto H, Kazuki Y, Takashima S, Oshimura M, Toyokuni S and Shinohara T.

Cell Stem Cell 5 巻頁： 76-86 2009年7月

Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenic defects. 査読有り国際誌

Takashima S, Takehashi M, Lee J, Chuma S, Okano M, Hata K, Suetake I, Nakatsuji N, Miyoshi H, Tajima S, Tanaka Y, Toyokuni S, Sasaki H, Kanatsu-Shinohara M, Shinohara T

Biology of reproduction 81 巻 ( 1 ) 頁： 155 - 64 2009年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biology of Reproduction

Although spermatogonial stem cells (SSCs) are committed to spermatogenesis, they may also convert to an embryonic stem cell-like pluripotent state at a low frequency. Because changes in DNA methylation patterns are associated with this conversion, we examined the effect of manipulating DNA methyltransferase (Dnmt) expression on the fate of cultured SSCs, germline stem (GS) cells. Dnmt1 knockdown induced apoptosis in GS cells, which was attenuated by the loss of Trp53. In contrast, GS cells proliferated normally in vitro after Dnmt3a/Dnmt3b ablation or during Dnmt3l overexpression. However, Dnmt3a/Dnmt3b double-mutant cells showed hypomethylation in the SineB1 repetitive sequence, and Dnmt3l-overexpressing cells showed hypermethylation in major and minor satellite sequences; neither cell type formed teratomas and completed spermatogenesis following transplantation into the seminiferous tubules. Although genetic manipulation did not increase the conversion of GS cells to a pluripotent state, these results underscore the important role of DNMTs in survival and spermatogenic differentiation in SSCs. © 2009 by the Society for the Study of Reproduction, Inc.

DOI： 10.1095/biolreprod.108.074708

Proapoptotic Effects of Dietary (n-3) Fatty Acids Are Enhanced in Colonocytes of Manganese-Dependent Superoxide Dismutase Knockout Mice 国際誌 Open Access

Fan, YY; Zhan, Y; Aukema, HM; Davidson, LA; Zhou, L; Callaway, E; Tian, Y; Weeks, BR; Lupton, JR; Toyokuni, S; Chapkin, RS

JOURNAL OF NUTRITION 139 巻 ( 7 ) 頁： 1328 - 1332 2009年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Nutrition

We recently demonstrated that (n-3) PUFA trigger the induction of apoptosis in the colon by enhancing phospholipid oxidation and mitochondrial Ca 2+ accumulation. To further elucidate the mechanisms regulating oxidative stress-induced apoptosis in vivo, a 2 x 2 experiment was designed using both wild type (control) and manganese-dependent superoxide dismutase (SOD2) heterozygous knockout mice (SOD2+/-), which exhibit increased mitochondrial oxidative stress. Mice were fed diets differing only in the type of fat [corn oil or fish oil containing (n-3) PUFA] at 15% by weight for 4 wk. Dietary (n-3) PUFA treatment enhanced (22%) apoptosis in colonic crypts. In addition, SOD2 haploinsufficiency enhanced (20%) apoptosis, which was further increased (36%) by (n-3) PUFA feeding. Dietary lipid source and genotype interactively modulated nitrotyrosine levels (P = 0.027) and inflammation (P = 0.032). These findings demonstrate that the proapoptotic effects of (n-3) PUFA are enhanced in oxidatively stressed SOD2+/- mice. Thus, (n-3) PUFA appear to promote an oxidation-reduction imbalance in the intestine, which may directly or indirectly trigger apoptosis and thereby reduce colon cancer risk. © 2009 American Society for Nutrition.

DOI： 10.3945/jn.109.106203

The potential role of reactive oxygen species in mammary neoplasm 査読有り国際誌

Arafah M., Khabaz M., Toyokuni S.

Australian Journal of Basic and Applied Sciences 3 巻 ( 3 ) 頁： 2949 - 2954 2009年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Australian Journal of Basic and Applied Sciences

The current study investigated the presence of oxidative stress markers (8-OHdG and HNE) in breast carcinoma in females from Saudi Arabia, and to examine the growth modulatory effects of HNE (induce cell growth inhibition) by measuring the expression of Ki-67 protein (cell proliferation antigen). Furthermore, to record if there is any significant prognostic indicator of these markers. In order to estimate the level of oxidative damage in breast cancer, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (HNE) expressions were investigated in breast carcinoma and benign lesions of breast, and were estimated by semi-quantitative immunohistochemical method. The observations of the present study showed that the level of expressions of 8-OHdG and HNE were significantly higher than those in controls. Reduction of oxidative stress is thought to be a very important measure for primary prevention of breast carcinoma. © 2009, INSInet Publication.

Scopus

The potential role of reactive oxygen species in mammary neoplasm 国際誌

Arafah M, Khabaz M, Toyokuni S

Australian Journal of Basic and Applied Sciences 3 巻 ( 3 ) 頁： 2949 - 2954 2009年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Australian Journal of Basic and Applied Sciences

researchmap

Pro-apoptotic effects of dietary (n-3) fatty acids are enhanced in colonocytes of SOD2 knockout mice. 査読有り

Fan YY, Zhan Y, Aukema HM, Davidson LA, Zhou L, Callaway E, Tian Y, Weeks BR, Lupton JR, Toyokuni S, Chapkin RS.

J. Nutr. 139 巻頁： 1328-1332 2009年5月

Effect of edaravone, a novel free radical scavenger, supplemented to cardioplegia on myocardial function after cardioplegic arrest: in vitro study of isolated rat heart. 査読有り

Yamazaki K, Miwa S, Toyokuni S, Nemoto S, Oriyanhan W, Takaba K, Saji Y, Marui A, Nishina T, Ikeda T and Komeda M.

Heart Vessels 24 巻頁： 228-235 2009年5月

Effect of edaravone, a novel free radical scavenger, supplemented to cardioplegia on myocardial function after cardioplegic arrest: in vitro study of isolated rat heart 査読有り

Yamazaki, K; Miwa, S; Toyokuni, S; Nemoto, S; Oriyanhan, W; Takaba, K; Saji, Y; Marui, A; Nishina, T; Ikeda, T; Komeda, M

HEART AND VESSELS 24 巻 ( 3 ) 頁： 228 - 235 2009年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Heart and Vessels

Cardioplegic arrest has been the main mechanism of myocardial protection during open-heart surgery; however, it causes myocardial injury during ischemia-reperfusion. Free radical scavengers are widely known to attenuate ischemia-reperfusion injury in various settings. We investigated the effects of edaravone, a novel free radical scavenger that was originally used for cerebral protection, on myocardial function during ischemia-reperfusion after cardioplegic arrest. Rat hearts were excised and perfused using Langendorff apparatus. The hearts were cardioplegically arrested for 90 min using St. Thomas' Hospital cardioplegic solution (ST solution) at 4°C every 45 min and then reperfused for 20 min. The hearts were divided into 4 groups (n = 13 in each group). In Group ST, the hearts were arrested using the ST solution alone. In Groups L, M, and H, the hearts were arrested using the ST solution supplemented with a low-dose (1 μM), moderate dose (10 μM), and high dose (100 μM) of edaravone, respectively. Left ventricular function (+dp/dt max) and the levels of the cardiac enzymes released were measured before and after cardioplegic arrest. At the end of the study, the water content and the tissue oxidative stress (8-hydroxy-2′-deoxyguanosine) of the heart were measured. During reperfusion, the edaravone-treated groups showed a greater functional recovery with regard to the +dp/dtmax (P < 0.05). The lactate level was the lowest (P < 0.01) in Group M. The water content of the hearts in the edaravone-treated groups was significantly lower (P< 0.05) than that in Group ST. Oxidative stress was significantly lower (P< 0.01) in the edaravone-treated hearts than in Group ST, and it was the lowest in Group M. The addition of edaravone to the cardioplegic solution ameliorates the impairment in myocardial function by reducing the oxidative stress after cardioplegic arrest. In this study, the maximum improvement in the myocardial function was achieved by addition of a moderate dose (10 μ) of edaravone. © Springer Japan 2009.

DOI： 10.1007/s00380-008-1106-1

Pro-apoptotic effects of dietary (n-3) fatty acids are enhanced in colonocytes of SOD2 knockout mice. 査読有り国際誌

Fan YY, Zhan Y, Aukema HM, Davidson LA, Zhou L, Callaway E, Tian Y, Weeks BR, Lupton JR, Toyokuni S, Chapkin RS

J. Nutr. 139 巻頁： 1328-1332 2009年5月

Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury. 査読有り

Hiraumi Y, Iwai-Kanai E, Baba S, Yui Y, Kamitsuji Y, Mizushima Y, Matsubara H, Watanabe M, Watanabe KI, Toyokuni S, Matsubara H, Nakahata T, Adachi S.

Am. J. Physiol. Heart Circ. Physiol. 296 巻頁： H823-H832 2009年3月

Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury 査読有り国際誌 Open Access

Hiraumi, Y; Iwai-Kanai, E; Baba, S; Yui, Y; Kamitsuji, Y; Mizushima, Y; Matsubara, H; Watanabe, M; Watanabe, K; Toyokuni, S; Matsubara, H; Nakahata, T; Adachi, S

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 296 巻 ( 3 ) 頁： H823 - H832 2009年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Physiology - Heart and Circulatory Physiology

Although granulocyte colony-stimulating factor (G-CSF) reportedly plays a cardiopro- tective role in several models of cardiac injury, clinical use of this drug in cardiac patients has been controversial. Here, we tested, in vivo and in vitro, the effect of G-CSF on cardiac mitochondria, which play a key role in determining cardiac cellular fate and function. Mild stimulation of C57/BL6 mice with doxorubicin (Dox) did not induce cardiac apoptosis or fibrosis but did induce damage to mitochondrial organization of the myocardium as observed through an electron microscope. Cardiac catheterization and echocardiography revealed that Dox did not alter cardiac systolic function or left ventricular size but did reduce diastolic function, an early sign of cardiac damage. Treatment with G-CSF attenuated significantly the damage to mitochondrial organization and rescued diastolic function. In an in vitro model for rat neonatal cardiomyocytes, a subapoptotic dose of Dox induced severe mitochondrial damage, including marked swelling of the cardiac mitochondria and/or decreased mitochondrial membrane potential. These mitochondrial changes were completely blocked by pretreatment with G-CSF. In addition, G-CSF dramatically improved ATP generation, which rescued Dox-impaired mitochondrial electron transport and oxygen consumption mainly through complex IV. These findings clearly indicate that G-CSF protects cardiac mitochondria, which are key organelles in the determination of cardiac cellular fate, in the early phase of cardiac injury. © 2009 the American Physiological Society.

DOI： 10.1152/ajpheart.00774.2008

Mechanisms of asbestos-induced carcinogenesis. Open Access

Toyokuni S.

Nagoya J. Med. Sci. 71 巻頁： 1-10 2009年2月

MECHANISMS OF ASBESTOS-INDUCED CARCINOGENESIS 国際誌 Open Access

Toyokuni Shinya

NAGOYA JOURNAL OF MEDICAL SCIENCE 71 巻 ( 1-2 ) 頁： 1 - 10 2009年2月

MECHANISMS OF ASBESTOS-INDUCED CARCINOGENESIS Open Access

TOYOKUNI S.

Nagoya Journal of Medical Science 71 巻 ( 1 ) 頁： 1 - 10 2009年2月

掲載種別：研究論文（学術雑誌）出版者・発行元：名古屋大学

Respiratory exposure to asbestos fibers has been associated with diffuse malignant mesothelioma (DMM) in humans. Despite advancements in the molecular analyses of human DMM and the development of animal models, the carcinogenic mechanisms of the disease remain unclear. There are basically three hypotheses regarding the pathogenesis of asbestos-induced DMM, which may be summarized as follows: (1) the "oxidative stress theory" is based on the fact that phagocytic cells that engulf asbestos fibers produce large amounts of free radicals due to their inability to digest the fibers, and epidemiological studies indicating that iron-containing asbestos fibers appear more carcinogenic; (2) the "chromosome tangling theory" postulates that asbestos fibers damage chromosomes when cells divide; and (3) the "theory of adsorption of many specific proteins as well as carcinogenic molecules" states that asbestos fibers in vivo concentrate proteins or chemicals including the components of cigarette smoke. Elucidation of the major mechanisms underlying DMM would be helpful for the development of novel strategies to prevent DMM induction in people who have already been exposed to asbestos.

DOI： 10.18999/nagjms.71.1-2.1

Open Access

CiNii Research

　前のページ - 次のページ　

<豊國 伸哉>

論文 - 豊國 伸哉

<豊國　伸哉>

論文 - 豊國　伸哉