Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Mth1 deficiency provides longer survival upon intraperitoneal crocidolite injection in female mice Reviewed International journal

Funahashi S.

Free Radical Research Vol. 54 ( 2-3 ) page： 195 - 205 2020.3

アスベストは卵巣表層上皮に鉄過剰状態を形成し卵巣がんの発がんに関わる

本岡大社, 伊藤文哉, 豊國伸哉

日本病理学会会誌 Vol. 109 ( 1 ) page： 314 - 314 2020.3

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway International journal

Yoshikawa Nobuhisa, Liu Wenting, Nakamura Kae, Yoshida Kosuke, Ikeda Yoshiki, Tanaka Hiromasa, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka, Kajiyama Hiroaki

SCIENTIFIC REPORTS Vol. 10 ( 1 ) 2020.1

Augmented oxidative stress increases 8-oxoguanine preferentially in the transcriptionally active genomic regions Reviewed International journal

Akatsuka S.

Free Radical Research 2020

Oxidative stress-dependent and -independent death of glioblastoma cells induced by non-thermal plasma-exposed solutions Reviewed International journal

Tanaka Hiromasa, Mizuno Masaaki, Katsumata Yuko, Ishikawa Kenji, Kondo Hiroki, Hashizume Hiroshi, Okazaki Yasumasa, Toyokuni Shinya, Nakamura Kae, Yoshikawa Nobuhisa, Kajiyama Hiroaki, Kikkawa Fumitaka, Hori Masaru

SCIENTIFIC REPORTS Vol. 9 ( 1 ) page： 13657 2019.9

How iron is handled in the course of heme catabolism: Integration of heme oxygenase with intracellular iron transport mechanisms mediated by poly (rC)-binding protein-2. International journal

Yanatori I, Richardson DR, Toyokuni S, Kishi F

Archives of biochemistry and biophysics Vol. 672 page： 108071 2019.9

Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia. Reviewed International journal

Zan Li, Li Jiang, Shan Hwu Chew, Tasuku Hirayama, Yoshitaka Sekido, Shinya Toyokuni

Redox biology Vol. 26 page： 101297 - 101297 2019.9

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

Hypoxia and acidity provide microenvironment for selection under evolutionary pressure and proliferation in cancer cells. Carbonic anhydrases (CAs) are a superfamily of metalloenzymes present in all life kingdoms, equilibrating the reactions among CO2, bicarbonate and H+. CA9, a membrane-associated α-CA, has been a drug target for various cancers. Whereas iron is essential not only for cancer cells but also for all the lives on earth, little is known on the association among hypoxia, iron metabolism, extracellular acidity and redox regulation. Malignant mesothelioma (MM), an aggressive tumor with poor prognosis, is an intriguing model in that asbestos-associated pathogenesis includes excess iron environment during carcinogenesis. Re-analysis of rat asbestos-induced MM model revealed an inverse association between high CA9 expression and survival. Here we used human MMs to identify the molecular events surrounding CA9 from the viewpoint of iron metabolism. CA9 expression was significantly higher in MM cells than in MeT-5A mesothelial cells, which was further amplified under hypoxia (1%O2) with increased catalytic Fe(II). CA9 suppression by inhibitors (S4 and U104) decreased viability and migration of MM cells, accompanied by overexpression of TFRC, IREB1/2 and FPN1(SLC40A1) and by downregulation of FTH/FTL. This expressional pattern was similar to that of erastin-induced ferroptosis in the same cells. Furthermore, we observed mitochondrial fission and enhanced autophagy with increased catalytic Fe(II) in both mitochondria and lysosomes after CA9 inhibition, accompanied by increased peroxides, mitochondrial O2- and lipid peroxidation. The eventual cell death was significantly inhibited by deferoxamine, ferrostatin-1 and Z-VAD-FMK, suggesting a mixed cell death of ferroptosis and apoptosis. Therefore, CA9 plays a role in equilibrating among hypoxia, iron metabolism and redox regulation in MM cells.

DOI： 10.1016/j.redox.2019.101297

アスベストは鉄過剰環境を形成し卵巣癌の発癌に関わる(Asbestos contributes to ovarian carcinogenesis via iron overload)

本岡大社, 伊藤文哉, 田代浩徳, 片渕秀隆, 豊國伸哉

日本癌学会総会記事 Vol. 78回 page： E - 1077 2019.9

l-Dehydroascorbic acid recycled by thiols efficiently scavenges non-thermal plasma-induced hydroxyl radicals Reviewed International journal

Yasumasa Okazaki, Hiromasa Tanaka, Masaru Hori, Shinya Toyokuni

Archives of Biochemistry and Biophysics Vol. 669 page： 87 - 95 2019.7

アスベストの曝露は上皮性悪性卵巣腫瘍の発癌に関与する

水野勇太, 本岡大社, 豊國伸哉

日本病理学会会誌 Vol. 108 ( 1 ) page： 460 - 461 2019.4

A scrutiny of circulating microRNA biomarkers for drug-induced tubular and glomerular injury in rats.

Toxicology Vol. 415 page： 26-36 2019.3

Non-thermal plasma-activated medium modified metabolomic profiles in the glycolysis of U251SP glioblastoma International journal

Kurake Naoyuki, Ishikawa Kenji, Tanaka Hiromasa, Hashizume Hiroshi, Nakamura Kae, Kajiyama Hiroaki, Toyokuni Shinya, Kikkawa Fumitaka, Mizuno Masaaki, Hori Masaru

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS Vol. 662 page： 83 - 92 2019.2

Twist1 was detected in mesenchymal cells of mammary fibroadenoma and invasive components of breast carcinoma in rats.

Funahashi S, Okazaki Y, Nagai H, Chew SH, Ogawa K, Toyoda T, Cho YM, Toyokuni S

Journal of toxicologic pathology Vol. 32 ( 1 ) page： 19-26 2019.1

Non-thermal plasma specifically kills oral squamous cell carcinoma cells in a catalytic Fe(II)-dependent manner Reviewed International journal

Kotaro Sato, Lei Shi, Fumiya Ito, Yuuki Ohara, Yashiro Motooka, Hiromasa Tanaka, Masaaki Mizuno, Masaru Hori, Tasuku Hirayama, Hideharu Hibi, Shinya Toyokuni

Journal of Clinical Biochemistry and Nutrition Vol. 65 ( 4 ) page： 8 - 15 2019

Iron Metabolism and Ferroptosis Reviewed International journal

Toyokuni Shinya, Yanatori Izumi

FERROPTOSIS IN HEALTH AND DISEASE page： 27 - 41 2019

A scrutiny of circulating microRNA biomarkers for tubular and glomerular injury in rats

KAGAWA Takumi, ZÁRYBNICKÝ Tomáš, OMI Takanao, SHIRAI Yuji, TOYOKUNI Shinya, ODA Shingo, YOKOI Tsuyoshi

Annual Meeting of the Japanese Society of Toxicology Vol. 46 ( 0 ) page： P - 233 2019

Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Toxicology

[Introduction] Drug-induced acute kidney injury (AKI) is a frequent cause of adverse drug reaction. Serum creatinine (CRE) and blood urea nitrogen (BUN) are widely used as standard biomarkers for kidney injury; however, the sensitivity and specificity are considered to be low. In recent years, circulating microRNA (miRNAs) have been attracting considerable attention as novel biomarkers for organ injury, but there are currently no established miRNA biomarkers for drug-induced AKI. The present study aimed to identify plasma miRNAs that may enable early and specific detection of drug-induced tubular and glomerular injury through next-generation sequencing analysis. [Methods] Six-week old male Sprague-Dawley rats were administered cisplatin and gentamicin to induce tubular injury. To create glomerular injury models, puromycin and doxorubicin were administered, and these models were always accompanied by tubular damage. Small RNA-sequencing was performed to analyze time-dependent changes in the plasma miRNA profiles. [Results and Discussion] In the differential analysis, miR-3473 was specifically up-regulated in the glomerular injury models. miR-143-3p and miR-122-5p were commonly down-regulated in all models, and the changes were earlier than the traditional biomarkers, such as plasma CRE and BUN. These data indicated that changes in the specific miRNAs in plasma may enable the early and sensitive detection of tubular and glomerular injuries. The present study suggests the potential utility of plasma miRNAs in the early and type-specific detection of drug-induced AKI.

DOI： 10.14869/toxpt.46.1.0_P-233

Chemiluminescence imaging of UVA induced reactive oxygen species in mouse skin using L-012 as a probe

Liu Jiao-Li, Xue Qiao, Liu Chen-Guang, Bai Feng-Wu, Wada Satoshi, Wang Jin-Ye

FREE RADICAL RESEARCH Vol. 52 ( 11-12 ) page： 1424 - 1431 2018.12

Analysis of the involvement of cancer-associated fibroblasts in the progression of malignant mesothelioma

Ohara Yuuki, Enomoto Atsushi, Takahashi Masahide, Toyokuni Shinya

CANCER SCIENCE Vol. 109 page： 454-454 2018.12

Multifaceted roles of Ptger2 (Prostaglandin E receptor 2) in asbestos-induced inflammation and malignant mesothelioma

Jiang Li, Akatsuka Shinya, Toyokuni Shinya

CANCER SCIENCE Vol. 109 page： 830-830 2018.12

Inflammatory microenvironment derived from asbestos increases mutagenesis to repairing mesothelial cell

Ito Fumiya, Toyokuni Shinya

CANCER SCIENCE Vol. 109 page： 830 - 830 2018.12

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Papers - TOYOKUNI Shinya