Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Possible involvement of iron-induced oxidative insults in neurodegeneration Reviewed International journal

Takeshi Asano, Masato Koike, Shin-ichi Sakata, Yukiko Takeda, Tomoko Nakagawa, Taku Hatano, Satoshi Ohashi, Manabu Funayama, Kenji Yoshimi, Masato Asanuma, Shinya Toyokuni, Hideki Mochizuki, Yasuo Uchiyama, Nobutaka Hattori, Kazuhiro Iwai

NEUROSCIENCE LETTERS Vol. 588 ( 1 ) page： 29 - 35 2015.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Involvement of iron in the development of neurodegenerative disorders has long been suggested, and iron that cannot be stored properly is suggested to induce iron toxicity. To enhance iron uptake and suppress iron storage in neurons, we generated transgenic (Tg) mice expressing iron regulatory protein 2 (IRP2), a major regulator of iron metabolism, in a neuron-specific manner. Although very subtle, IRP2 was expressed in all regions of brain examined. In the Tg mice, mitochondrial oxidative insults were observed including generation of 4-hydroxynonenal modified proteins, which appeared to be removed by a mitochondrial quality control protein Parkin. Inter-crossing of the Tg mice to Parkin knockout mice perturbed the integrity of neurons in the substantia nigra and provoked motor symptoms. These results suggest that a subtle, but chronic increase in IRP2 induces mitochondrial oxidative insults and accelerates neurodegeneration in a mouse model of Parkinson's disease. Thus, the IRP2 Tg may be a useful tool to probe the roles of iron-induced mitochondrial damages in neurodegeraration research. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2014.12.052

MINIMAL INFLAMMOGENICITY OF PRISTINE SINGLE-WALL CARBON NANOTUBES Reviewed International journal

Shinya Toyokuni, Li Jiang, Ryo Kitaura, Hisanori Shinohara

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 77 ( 1-2 ) page： 195 - 202 2015.2

Language：English Publishing type：Research paper (scientific journal) Publisher：NAGOYA UNIV, SCH MED

Carbon nanotubes (CNTs) are a novel synthetic material comprising only carbon atoms. Based on its rigidity, its electrical and heat conductivity and its applicability to surface manufacturing, this material is expected to have numerous applications in industry. However, due to the material's dimensional similarity to asbestos fibers, its carcinogenicity was hypothesized during the last decade, and indeed, we have shown that multi- wall CNTs (MWCNTs) of 50 nm in diameter are potently carcinogenic to mesothelial cells after intraperitoneal injection. Additionally, we suggested that inflammogenicity after intraperitoneal injection can predict mesothelial carcinogenesis. However, few data have been published on the intraperitoneal inflammogenicity of single-wall CNTs (SWCNTs). Here, we conducted a series of studies on SWCNTs using both intraperitoneal injection into rats and MeT5A mesothelial cells. Intraperitoneal injection of 10 mg SWCNTs caused no remarkable inflammation in the abdominal cavity, and the exposure of MeT5A cells to up to 25 mu g/cm(2) SWCNTs did not alter proliferation. MWCNTs of 50 nm in diameter were used as a positive control, and tangled MWCNTs of 15 nm in diameter were used as a negative control. The results suggest that SWCNTs are a low- risk material with respect to mesothelial carcinogenesis.

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Minimal inflammogenicity of pristine single-wall carbon nanotubes.

Toyokuni S, Jiang LI, Kitaura R, Shinohara H

Nagoya journal of medical science Vol. 77 ( 1-2 ) page： 195 - 202 2015.2

Minimal inflammogenicity of pristine single-wall carbon nanotubes.

Toyokuni S, Jiang LI, Kitaura R, Shinohara H

Nagoya journal of medical science Vol. 77 ( 1-2 ) page： 195 - 202 2015.2

MINIMAL INFLAMMOGENICITY OF PRISTINE SINGLE-WALL CARBON NANOTUBES

Toyokuni Shinya, Jiang Li, Kitaura Ryo, Shinohara Hisanori

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 77 ( 1-2 ) page： 195 - 202 2015.2

Catalytic ferrous iron in amniotic fluid as a predictive marker of human maternal-fetal disorders. Reviewed

Yuka Hattori, Takahiro Mukaide, Li Jiang, Tomomi Kotani, Hiroyuki Tsuda, Yukio Mano, Seiji Sumigama, Tasuku Hirayama, Hideko Nagasawa, Fumitaka Kikkawa, Shinya Toyokuni

Journal of clinical biochemistry and nutrition Vol. 56 ( 1 ) page： 57 - 63 2015.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SOCIETY FOR FREE RADICAL RESEARCH JAPAN

Amniotic fluid contains numerous biomolecules derived from fetus and mother, thus providing precious information on pregnancy. Here, we evaluated oxidative stress of human amniotic fluid and measured the concentration of catalytic Fe(II). Amniotic fluid samples were collected with consent from a total of 89 subjects in Nagoya University Hospital, under necessary medical interventions: normal pregnancy at term, normal pregnancy at the 2nd trimester, preterm delivery with maternal disorders but without fetal disorders, congenital diaphragmatic hernia, fetal growth restriction, pregnancy-induced hypertension, gestational diabetes mellitus, Down syndrome and trisomy 18. Catalytic Fe(II) and oxidative stress markers (8-hydroxy-2'-deoxyguanosine, 8-OHdG; dityrosine) were determined with RhoNox-1 and specific antibodies, respectively, using plate assays. Levels of 8-OHdG and dityrosine were higher in the 3rd trimester compared with the 2nd trimester in normal subjects, and the abnormal groups generally showed lower levels than the controls, thus suggesting that they represent fetal metabolic activities. In contrast, catalytic Fe(II) was higher in the 2nd trimester than the 3rd trimester in the normal subjects, and overall the abnormal groups showed higher levels than the controls, suggesting that high catalytic Fe(II) at late gestation reflects fetal pathologic alterations. Notably, products of H2O2 and catalytic Fe(II) remained almost constant in amniotic fluid.

DOI： 10.3164/jcbn.14-82

Napsin A is a specific marker for ovarian clear cell adenocarcinoma. Reviewed International journal

Yoriko Yamashita, Tetsuro Nagasaka, Aya Naiki-Ito, Shinya Sato, Shugo Suzuki, Shinya Toyokuni, Masafumi Ito, Satoru Takahashi

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Vol. 28 ( 1 ) page： 111 - 7 2015.1

Language：English Publishing type：Research paper (scientific journal)

Ovarian clear cell adenocarcinoma has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Differential diagnosis of clear cell adenocarcinoma from other ovarian surface epithelial tumors is important for its treatment. Napsin A is a known diagnostic marker for lung adenocarcinoma, and expression of napsin A is reported in a certain portion of thyroid and renal carcinomas. However, napsin A expression in ovarian surface epithelial tumors has not previously been examined. In this study, immunohistochemical analysis revealed that in 71 of 86 ovarian clear cell adenocarcinoma patients (83%) and all of the 13 patients with ovarian clear cell adenofibroma, positive napsin A staining was evident. No expression was observed in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19 endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10 mucinous adenocarcinomas, or 3 yolk sac tumors of the ovary. Furthermore, expression of napsin A was not observed in the normal surface epithelium of the ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical epithelium, or the endometrium of the uterus. Therefore, we propose that napsin A is another sensitive and specific marker for distinguishing ovarian clear cell tumors (especially adenocarcinomas) from other ovarian tumors.

DOI： 10.1038/modpathol.2014.61

Aging rather than sun exposure is a major determining factor for the density of miR-125b-positive epidermal stem cells in human skin. Reviewed

Toyokuni S, Jiang L, Wang S, Hirao A, Wada T, Soh C, Tohyama K and Kawada A.

Pathol Int Vol. 65 page： 415-419 2015

Malignant mesothelioma as an oxidative stress-induced cancer: An update. Reviewed

Chew SH and Toyokuni S.

Free Radic Biol Med Vol. 86 page： 166-178 2015

Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury. Reviewed

Hattori Y, Kotani T, Tsuda H, Mano Y, Rei T, Li H, Hirako S, Ushida T, Imai K, Nakano T, Sato Y, Miki R, Sumigama S, Iwase A, Toyokuni S and Kikkawa F.

Free Radic Res Vol. 49 page： 1026-1037 2015

Possible involvement of iron-induced oxidative insults in neurodegeneration. Reviewed

Asano T, Koike M, Sakata S, Takeda Y, Nakagawa T, Hatano T, Ohshi S, Funayama M, Yoshimi K, Sanuma M, Toyokuni S, Mochizuki H, Uchiyama Y, Hattori N and Iwai K.

Neurosci Lett Vol. 588 page： 29-35 2015

Receptor role of annexin A2 in the mesothelial endocytosis of crocidolite fibers. Reviewed

Yamashita K, Nagai H and Toyokuni S.

Lab Invest Vol. 95 page： 749-764 2015

Minimal inflammogenicity of pristine single-wall carbon nanotubes. Reviewed

Toyokuni S, Jiang L, Kitaura R and Shinohara S.

Nagoya J Med Sci Vol. 77 page： 195-202 2015

Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells. Reviewed

Funahashi F, Okazaki Y, Ito D, Asakawa A, Nagai H, Tajima M and Toyokuni S.

J Clin Biochem Nutr 56: 111-117, 2015. Vol. 56 page： 111-117 2015

Catalytic ferrous iron in amniotic fluid as a predictive marker of human maternal-fetal disorders. Reviewed

Hattori Y, Mukaide T, Jiang L, Kotani T, Tsuda H, Mano Y, Sumigama S, Hirayama T, Nagasawa H, Kikkawa F and Toyokuni S.

J Clin Biochem Nutr 56: 57-63, 2015. Vol. 56 page： 57-63 2015

Napsin A is a specific marker for ovarian clear cell adenocarcinoma. Reviewed

Yamashita Y, Nagasaka T, Naiki-Ito A, Sato S, Suzuki S, Toyokuni S, Ito M and Takahashi S.

Mod Pathol Vol. 28 page： 111-117 2015

Application of intermittent microwave irradiation to western blot analysis. Reviewed

Liu YT, Toyokuni S.

Methods Mol Biol Vol. 1314 page： 185-190 2015

Chemical conversion of human fibroblasts into neuronal cells: dawn of future clinical trials. Invited

Toyokuni S.

J Clin Biochem Nutr Vol. 56 page： 165 2015

A trial to find appropriate animal models of dichloropropane-induced cholangiocarcinoma based on the hepatic distribution of glutathione S-transferases. Reviewed

Zhang L, Zong C, Ichihara S, Naito H, Toyokuni S, Kumagai S, Ichihara G.

J Occup Health. Vol. 57 ( 6 ) page： 548-554 2015

A trial to find appropriate animal models of dichloropropane-induced cholangiocarcinoma based on the hepatic distribution of glutathione S-transferases International journal

Zhang Lingyi, Zong Cai, Ichihara Sahoko, Naito Hisao, Toyokuni Shinya, Kumagai Shinji, Ichihara Gaku

Journal of Occupational Health Vol. 57 ( 6 ) page： 548 - 554 2015

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Society for Occupational Health

Objectives: It has been reported that 1,2-Dichloropropane (DCP) induced cholangiocarcinoma (CCA) in offset color proof-printing workers. However, exposure to DCP by inhalation or gavage for 2 year did not induce CCA in mice and rats. The present study mapped the hepatic distribution of GST, which is known to activate dihalogenated alkanes, and proliferative and fibrotic changes in bile ducts in various species to find the most appropriate animal model of DCP-induced CCA. Methods: First, 12 each of C57BL/6J mice, Balb/cA mice, F344 rats, Syrian hamsters, and guinea pigs were divided into four equal groups and exposed to DCP at 0, 300, 1,000, or 3,000 ppm 8 hours/day for 7 days. Second, 32 Balb/cA mice and 32 Syrian hamsters were each divided into four equal groups and exposed to DCP at 0, 200, 400, and 800 ppm 6 hours/day for 14 days. After the last exposure, the animals were decapitated, and the livers were dissected out for histopathological evaluation. Immunostaining was conducted to determine the distribution of GSTT1, GSTM1, and GSTPi, as well as the expression of proliferation marker Ki67. Results: GSTT1, GSTM1, and GSTPi were expressed in both hepatocytes and bile duct cells in all control and exposed animals. There was no clear difference in the expression of Ki67 between the exposed groups and the control. No fibrotic changes were observed in any species or strains examined. Conclusions: Expression of GSTT1 or other GST isozymes might not explain the difference in sensitivity of hepatocytes and the bile duct to DCP between humans and rodents.(J Occup Health 2015; 57: 548–554)

DOI： 10.1539/joh.15-0085-oa

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