Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Preliminary characterization of a murine model for 1-bromopropane neurotoxicity: Role of cytochrome P450. Reviewed

Zong C, Garner CE, Huang C, Zhang X, Zhang L, Chang J, Toyokuni S, Ito H, Kato M, Sakurai T, Ichihara S, Ichihara G.

Toxicol Lett. Vol. 258 page： 249-58 2016.9

Biphasic effects of l-ascorbate on the tumoricidal activity of non-thermal plasma against malignant mesothelioma cells. Reviewed

Shi L, Wang Y, Ito F, Okazaki Y, Tanaka H, Mizuno M, Hori M, Richardson DR, Toyokuni S.

Arch Biochem Biophys. Vol. 605 page： 106-16 2016.9

Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia. International journal

Shima Hirako, Hiroyuki Tsuda, Tomomi Kotani, Seiji Sumigama, Yukio Mano, Tomoko Nakano, Kenji Imai, Hua Li, Shinya Toyokuni, Fumitaka Kikkawa

Phytotherapy research : PTR Vol. 30 ( 9 ) page： 1474 - 80 2016.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Congenital diaphragmatic hernia (CDH) can induce lung hypoplasia and pulmonary hypertension and is associated with high mortality. The purpose of this study is to examine the efficacy and safety of antenatal Saireito (TJ-114), a traditional Japanese herbal medicine, in a rat CDH model. Sprague-Dawley rats were exposed to an herbicide (nitrofen, 100 mg) on embryonic day 9 (E9) to induce CDH, and antenatal Saireito (2000 mg/kg/day) was orally administered from E10 to E20. On E21, fetuses were delivered. Antenatal Saireito significantly decreased the incidence of CDH (p < 0.01), increased lung volume (p < 0.01), improved alveolarization and pulmonary artery remodeling using histological analysis, and improved respiratory function using gasometric analysis (pH; p < 0.05, and PCO2; p < 0.01). In addition, antenatal Saireito significantly decreased endothelin-1 and endothelin receptor A expression in the pulmonary arteries. Taken together, our results demonstrated that antenatal Saireito can improve fetal pulmonary hypoplasia and pulmonary vascular remodeling and, as a result, can improve respiratory function in a rat CDH model. Copyright (C) 2016 John Wiley & Sons, Ltd.

DOI： 10.1002/ptr.5645

Molecular hydrogen suppresses activated Wnt/beta-catenin signaling Reviewed International journal

Yingni Lin, Bisei Ohkawara, Mikako Ito, Nobuaki Misawa, Kentaro Miyamoto, Yasuhiko Takegami, Akio Masuda, Shinya Toyokuni, Kinji Ohno

SCIENTIFIC REPORTS Vol. 6 ( 6 ) page： 31986 2016.8

Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Molecular hydrogen (H-2) is effective for many diseases. However, molecular bases of H-2 have not been fully elucidated. Cumulative evidence indicates that H-2 acts as a gaseous signal modulator. We found that H-2 suppresses activated Wnt/beta-catenin signaling by promoting phosphorylation and degradation of beta-catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3-phosphorylation sites of beta-catenin abolished the suppressive effect of H-2. H-2 did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H-2 has no direct effect on GSK3 itself. Knockdown of adenomatous polyposis coli (APC) or Axin1, which form the beta-catenin degradation complex, minimized the suppressive effect of H2 on beta-catenin accumulation. Accordingly, the effect of H-2 requires CK1/GSK3-phosphorylation sites of beta-catenin, as well as the beta-catenin degradation complex comprised of CK1, GSK3, APC, and Axin1. We additionally found that H-2 reduces the activation of Wnt/beta-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H-2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating beta-catenin accumulation. We first demonstrate that H-2 suppresses abnormally activated Wnt/beta-catenin signaling, which accounts for the protective roles of H-2 in a fraction of diseases.

DOI： 10.1038/srep31986

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Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis. International journal

Fumiya Ito, Takahiro Nishiyama, Lei Shi, Masahiko Mori, Tasuku Hirayama, Hideko Nagasawa, Hiroyuki Yasui, Shinya Toyokuni

Biochemical and biophysical research communications Vol. 476 ( 4 ) page： 600 - 606 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Iron is an essential nutrient for every type of life on earth. However, excess iron is cytotoxic and can lead to an increased cancer risk in humans. Catalytic ferrous iron [Fe(II)] is an initiator of the Fenton reaction, which causes oxidative stress by generating hydroxyl radicals. Recently, it became possible to localize catalytic Fe(II) in situ with a turn-on fluorescent probe, RhoNox-1. Here, we screened each organ/cell of rats to globally evaluate the distribution of catalytic Fe(II) and found that eosinophils showed the highest abundance. In various cells, lysosomes were the major organelle, sharing 40-80% of RhoNox-1 fluorescence. We then used an ovalbumin-induced allergic peritonitis model to study the dynamics of catalytic Fe(II). Peritoneal lavage revealed that the total iron contents per cell were significantly decreased, whereas an increase in the number of inflammatory cells (macrophages, neutrophils, eosinophils and lymphocytes) resulted in an increased total iron content of the peritoneal inflammatory cells. Notably, macrophages, eosinophils and neutrophils exhibited significantly increased catalytic Fe(II) with increased DMT1 expression and decreased ferritin expression, though catalytic Fe(II) was significantly decreased in the peritoneal lavage fluid. In conclusion, catalytic Fe(II) in situ more directly reflects cellular activity and the accompanying pathology than total iron does. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2016.06.003

Molecular hydrogen suppresses activated Wnt/β-catenin signaling. Reviewed

Lin Y, Ohkawara B, Ito M, Misawa N, Miyamoto K, Takegami Y, Masuda A, Toyokuni S, Ohno K.

Sci Rep. Vol. 25 ( 6 ) page： 31986 2016.8

Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis. Reviewed

Ito F, Nishiyama T, Shi L, Mori M, Hirayama T, Nagasawa H, Yasui H, Toyokuni S.

Biochem Biophys Res Commun. Vol. 476 ( 4 ) page： 600-6 2016.8

The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology. Reviewed

Cahill MA, Jazayeri JA, Catalano SM, Toyokuni S, Kovacevic Z, Richardson DR.

Biochim Biophys Acta. 2016 Jul 22. Vol. pii: S0304-419X ( 16 ) page： 30049-X. 2016.7

Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis Reviewed International journal

Jiang Li, Chew Shan-Hwu, Nakamura Kosuke, Ohara Yuuki, Akatsuka Shinya, Toyokuni Shinya

CANCER SCIENCE Vol. 107 ( 7 ) page： 908 - 915 2016.7

Possible therapeutic option of aqueous plasma for refractory ovarian cancer Reviewed International journal

Kajiyama Hiroaki, Utsumi Fumi, Nakamura Kae, Tanaka Hiromasa, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka

CLINICAL PLASMA MEDICINE Vol. 4 ( 1 ) page： 14 - 18 2016.7

The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology. Reviewed International journal

Cahill MA, Jazayeri JA, Catalano SM, Toyokuni S, Kovacevic Z, Richardson DR

Biochim Biophys Acta. 2016 Jul 22. Vol. pii: S0304-419X ( 16 ) page： 30049-X. 2016.7

[Iron function and carcinogenesis].

Akatsuka S, Toyokuni S

Nihon rinsho. Japanese journal of clinical medicine Vol. 74 ( 7 ) page： 1168 - 75 2016.7

[Iron function and carcinogenesis].

Akatsuka S, Toyokuni S

Nihon rinsho. Japanese journal of clinical medicine Vol. 74 ( 7 ) page： 1168 - 75 2016.7

Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium. Reviewed

Vol. 35 ( 6 ) page： 3169-77 2016.6

Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis. Reviewed

Jiang L, Chew SH, Nakamura K, Ohara Y, Akatsuka S, Toyokuni S.

Cancer Sci. 2016 Jul;107(7):908-15. Vol. 107 ( 7 ) page： 908-15 2016.6

Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis. Reviewed International journal

Jiang L, Chew SH, Nakamura K, Ohara Y, Akatsuka S, Toyokuni S

Cancer Sci. 2016 Jul;107(7):908-15. Vol. 107 ( 7 ) page： 908-15 2016.6

Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium International journal

Fumi Utsumi, Hiroaki Kajiyama, Kae Nakamura, Hiromasa Tanaka, Masaaki Mizuno, Shinnya Toyokuni, Masaru Hori, Fumitaka Kikkawa

ONCOLOGY REPORTS Vol. 35 ( 6 ) page： 3169 - 77 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Non-thermal atmospheric pressure plasma has been widely studied in recent years in many fields, including cancer treatment. However, its efficiency for inducing apoptosis sometimes varies depending on the cell species and experimental conditions. The aim of this study was to elucidate what causes these differences in responses to plasma treatment. Using four ovarian cancer cell lines, the cell density had a markedly negative impact on the proliferation inhibition rate (PIR) and it was more obvious in OVCAR-3 and NOS2 cells. Furthermore, TOV21G and ES-2 cells were drastically sensitive to plasma-activated medium (PAM) compared with the other two cell lines. We demonstrated that the proportion of reactive oxygen species and cell number had a marked impact on the effect of PAM against ovarian cancer cells. Additionally it was suggested that the morphological features of cells were also closely related to the sensitivity of cancer cells to the plasma treatment.

DOI： 10.3892/or.2016.4726

The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy Reviewed International journal

Toyokuni S.

Pathology International Vol. 66 ( 5 ) page： 245 - 259 2016.5

The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy. Invited Reviewed International journal

Toyokuni S

Pathol Int. Vol. 66 ( 5 ) page： 245-259 2016.5

Oxidative stress as an iceberg in carcinogenesis and cancer biology Reviewed International journal

Toyokuni Shinya

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS Vol. 595 page： 46 - 49 2016.4

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Papers - TOYOKUNI Shinya