Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

Division display 41 - 60 of about 1,276 ／ All the affair displays >>

Role of Iron, Oxygen and Ferroptosis in Tumor Evolutionary Biology Reviewed International journal

Toyokuni, S; Kong, Y; Luo, Y; Zheng, H; Motooka, Y; Akatsuka, S

FREE RADICAL BIOLOGY AND MEDICINE Vol. 208 page： S112 - S112 2023.11

Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis. Reviewed International journal Open Access

Yamada K, Tazaki A, Ushio-Watanabe N, Usui Y, Takeda A, Matsunaga M, Suzumura A, Shimizu H, Zheng H, Ariefta NR, Yamamoto M, Hara H, Goto H, Sonoda KH, Nishiguchi KM, Kato M, Nishikawa Y, Toyokuni S, Kaneko H

Redox biology Vol. 67 page： 102890 2023.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Redox Biology

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.

DOI： 10.1016/j.redox.2023.102890

Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression. Reviewed International journal Open Access

Van San E, Debruyne AC, Veeckmans G, Tyurina YY, Tyurin VA, Zheng H, Choi SM, Augustyns K, van Loo G, Michalke B, Venkataramani V, Toyokuni S, Bayir H, Vandenabeele P, Hassannia B, Vanden Berghe T

Cell death and differentiation Vol. 30 ( 9 ) page： 2092 - 2103 2023.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Cell Death and Differentiation

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by central nervous (CNS) demyelination resulting in axonal injury and neurological deficits. Essentially, MS is driven by an auto-amplifying mechanism of inflammation and cell death. Current therapies mainly focus on disease modification by immunosuppression, while no treatment specifically focuses on controlling cell death injury. Here, we report that ferroptosis, an iron-catalyzed mode of regulated cell death (RCD), contributes to MS disease progression. Active and chronic MS lesions and cerebrospinal fluid (CSF) of MS patients revealed several signs of ferroptosis, reflected by the presence of elevated levels of (labile) iron, peroxidized phospholipids and lipid degradation products. Treatment with our candidate lead ferroptosis inhibitor, UAMC-3203, strongly delays relapse and ameliorates disease progression in a preclinical model of relapsing-remitting MS. In conclusion, the results identify ferroptosis as a detrimental and targetable factor in MS. These findings create novel treatment options for MS patients, along with current immunosuppressive strategies. [Figure not available: see fulltext.]

DOI： 10.1038/s41418-023-01195-0

Open Access

Scopus

PubMed

Organic decomposition and synthesis reactions in lactated solution exposed to nonequilibrium atmospheric pressure plasma Reviewed International journal Open Access

Liu, Y; Ishikawa, K; Tanaka, H; Miron, C; Kondo, T; Nakamura, K; Mizuno, M; Kajiyama, H; Toyokuni, S; Hori, M

PLASMA PROCESSES AND POLYMERS Vol. 20 ( 5 ) 2023.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Plasma Processes and Polymers

Lactate is used in the food and pharmaceutical industries and is a crucial intermediate for synthesis. Plasma-activated lactate (PAL) in Ringer's solution was recently shown to have effective antitumor action. Small molecule aldehydes, ketones, and organic acids were produced from lactate during plasma exposure, and five-membered conjugated lactone isomers of furanone (C<inf>5</inf>H<inf>6</inf>O<inf>2</inf>) were detected formed by interactions of lactate or its fragments with •OH, organic radicals, and H<inf>2</inf>O<inf>2</inf>. 2,3-Dimethyl-tartaric acid may be the effective component in PAL for the selective killing of cancer but not normal cells and possible pathways for its synthesis are provided. Aqueous reaction mechanisms are explained, including dehydration, esterification, hydrolysis, and dimerization. This study will help develop novel cancer therapies and further plasma organic chemistry.

DOI： 10.1002/ppap.202200193

Open Access

Web of Science

Scopus

Commentary on "Mechanisms of asbestos-induced carcinogenesis" published in 2009. Reviewed International journal Open Access

Toyokuni S

Nagoya journal of medical science Vol. 85 ( 1 ) page： 13 - 15 2023.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Nagoya Journal of Medical Science

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.85.1.13

Toward the next century of the Nagoya Journal of Medical Science: message from the Editor-in-chief. Reviewed International journal Open Access

Toyokuni S

Nagoya journal of medical science Vol. 85 ( 1 ) page： 1 - 4 2023.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Nagoya Journal of Medical Science

It is my great pleasure and honor as the Editor-in-chief to congratulate the centennial anniversary of the Nagoya Journal of Medical Science in 2023 with all the editorial board members and the technical staffs as well as the authors and the readers. One hundred years are quite a long period, and the persistent publication from a medical school of national university in Japan has not been so easy. Especially, the publication was suspended from 1940 to 1950 due to the World War II.

DOI： 10.18999/nagjms.85.1.1

BRCA1 haploinsufficiency promotes chromosomal amplification under renal carcinogenesis through ferroptosis-resistance Reviewed International journal

Kong, YY; Akatsuka, S; Motooka, Y; Zheng, H; Shiraki, Y; Mashimo, T; Imaoka, T; Toyokuni, S

CANCER SCIENCE Vol. 114 page： 1534 - 1534 2023.2

Cooperation of Poly(rC)-binding Proteins 1/2 and Glutathione in Ferroptosis Induced by Plasmaactivated Ringer's Lactate Reviewed International journal

Zheng, H; Jiang, L; Lyu, QY; Akatsuka, S; Motooka, Y; Sekido, Y; Nakamura, K; Tanaka, H; Ishikawa, K; Kajiyama, H; Mizuno, M; Hori, M; Toyokuni, S

CANCER SCIENCE Vol. 114 page： 1340 - 1340 2023.2

Cooperation of Poly(rC)-binding Proteins 1/2 and Glutathione in Ferroptosis Induced by Plasma-activated Ringer's Lactate Reviewed International journal

Zheng, H; Jiang, L; Lyu, QY; Akatsuka, S; Motooka, Y; Sekido, Y; Nakamura, K; Tanaka, H; Ishikawa, K; Kajiyama, H; Mizuno, M; Hori, M; Toyokuni, S

CANCER SCIENCE Vol. 114 page： 749 - 749 2023.2

Carcinogenic genome toxicity of environmental factors, asbestos and talc in ovary Reviewed International journal

Motooka, Y; Onimaru, K; Suzuki, HI; Katabuchi, M; Kondoh, E; Tashiro, H; Katabuchi, H; Toyokuni, S

CANCER SCIENCE Vol. 114 page： 1085 - 1085 2023.2

A/J mice exhibit a high susceptibility to ferric nitrilotriacetate-induced RCC through the resistance to ferroptosis Reviewed International journal

Akatsuka, S; Cheng, Z; Toyokuni, S

CANCER SCIENCE Vol. 114 page： 1315 - 1315 2023.2

Ferroptosis resistance is induced by BRCA1 deficiency in asbestos-induced mesothelioma Reviewed International journal

Luo, YG; Motooka, Y; Akatsuka, S; Mashimo, T; Imaoka, T; Toyokuni, S

CANCER SCIENCE Vol. 114 page： 1308 - 1308 2023.2

Validation of reduced ovarian reserve in BRCA1 haploinsufficient rats Reviewed International journal

Sonehara, R; Motooka, Y; Kajiyama, H; Mashimo, T; Imaoka, T; Toyokuni, S

CANCER SCIENCE Vol. 114 page： 2041 - 2041 2023.2

Precision cancer prevention Reviewed International journal

Toyokuni, S; Takayama, T

CANCER SCIENCE Vol. 114 page： 1528 - 1528 2023.2

Ferroptosis-resistance in rodent cancer models Reviewed International journal

Toyokuni, S; Kong, Y; Akatsuka, S; Motooka, Y; Zheng, H; Mashimo, T; Imaoka, T

CANCER SCIENCE Vol. 114 page： 912 - 912 2023.2

Plasma activated Ringer's lactate solution. Reviewed International journal Open Access

Tanaka H, Mizuno M, Ishikawa K, Miron C, Okazaki Y, Toyokuni S, Nakamura K, Kajiyama H, Hori M

Free radical research Vol. 57 ( 1 ) page： 14 - 20 2023.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Free Radical Research

Low-temperature plasma (LTP) has been widely used in life science. Plasma-activated solutions were defined as solutions irradiated with LTP, and water, medium, and Ringer’s solutions have been irradiated with LTP to produce plasma-activated solutions. They contain chemical compounds produced by reactions among LTP, air, and solutions. Reactive oxygen and nitrogen species (RONS) are major components in plasma-activated solutions and recent studies revealed that plasma-activated organic compounds are produced in plasma-activated Ringer’s lactate solution (PAL). Many in vitro and in vivo studies demonstrated that PAL exhibits anti-tumor effects on cancers, and biochemical analyses revealed intracellular molecular mechanisms of cancer cell death by PAL.

DOI： 10.1080/10715762.2023.2182663

Non-thermal plasma elicits ferrous chloride-catalyzed DMPO-OH. Reviewed International journal

Okazaki Y, Ito N, Tanaka H, Hori M, Toyokuni S

Free radical research Vol. 56 ( 9-10 ) page： 595 - 606 2022.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Free Radical Research

Non-thermal plasma (NTP) induces the generation of reactive oxygen species (ROS) and reactive nitrogen species, such as hydroxyl radicals (•OH), hydrogen peroxide (H<inf>2</inf>O<inf>2</inf>), singlet oxygen, superoxide, ozone, and nitric oxide, at near-physiological temperatures. These molecules promote blood coagulation, wound healing, disinfection, and selective cancer cell death. Based on these evidences, clinical trials of NTP have been conducted for treating chronic wounds and head and neck cancers. Although clinical applications have progressed, the stoichiometric quantification of NTP-induced ROS remains unclear in the liquid phase in the presence of FeCl<inf>2</inf> or FeCl<inf>3</inf> in combination with biocompatible reducing agents, which may modulate the final biological effects of NTP. In this study, we employed electron paramagnetic resonance spectroscopy to quantify ROS using spin-trapping probe, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and H<inf>2</inf>O<inf>2</inf>, using luminescent probe in the presence of FeCl<inf>2</inf> or FeCl<inf>3</inf>. NTP-induced DMPO-OH levels were elevated 10–100 µM FeCl<inf>2</inf> or 500 and 1000 µM FeCl<inf>3</inf>. NTP-induced DMPO-OH with 10 µM FeCl<inf>2</inf> or FeCl<inf>3</inf> was significantly scavenged by ascorbate, α-tocopherol, dithiothreitol, reduced glutathione, or oxidized glutathione, whereas dehydroascorbate was ineffective in 2 mM DMPO. NTP-induced H<inf>2</inf>O<inf>2</inf> was significantly degraded by 100 µM FeCl<inf>2</inf> and FeCl<inf>3</inf> in an iron-dependent manner. Meanwhile, decomposition of H<inf>2</inf>O<inf>2</inf> by catalase decayed DMPO-OH efficiently in the presence of iron, indicating iron causes DMPO-OH production and degradation simultaneously. These results suggest that NTP-induced DMPO-OH is generated by the H<inf>2</inf>O<inf>2</inf>-consuming, iron-dependent Fenton reaction and ferryl intermediates. The potential iron-mediated ROS production by NTP is also discussed to clarify the interaction between NTP-induced ROS and biomolecules.

DOI： 10.1080/10715762.2022.2157272

Web of Science

Scopus

PubMed

Editorial: Centennial anniversary of vitamin E discovery. Reviewed International journal

Toyokuni S, Noguchi N, Niki E

Free radical biology & medicine Vol. 183 page： 125 - 126 2022.4

BRCA1 deficiency regulates the metabolism of iron and oxidative stress-induced carcinogenesis in the kidney Reviewed International journal

Kong, YY; Motooka, Y; Akatsuka, S; Mashimo, T; Imaoka, T; Toyokuni, S

CANCER SCIENCE Vol. 113 page： 336 - 336 2022.2

Iron overload led by genital talc exposure contributes to ovarian carcinogenesis Reviewed International journal

Motooka, Y; Ito, F; Tashiro, H; Katabuchi, H; Toyokuni, S

CANCER SCIENCE Vol. 113 page： 725 - 725 2022.2

　 PREV - NEXT 　

<TOYOKUNI Shinya>

Papers - TOYOKUNI Shinya