研究者業績

田中 健一郎

タナカ ケンイチロウ  (Tanaka Ken-ichiro)

基本情報

所属
武蔵野大学 薬学部・薬学研究所 准教授
学位
学士(薬学)(岡山大学)
修士(薬学)(熊本大学大学院)
博士(薬学)(熊本大学大学院)

J-GLOBAL ID
201701002528091583
researchmap会員ID
B000271201

委員歴

 2

論文

 96
  • Masahiro Kawahara, Ken-Ichiro Tanaka, Midori Kato-Negishi
    Biomolecules 14(7) 2024年6月28日  査読有り
    Zinc (Zn) and copper (Cu) are essential for normal brain functions. In particular, Zn and Cu are released to synaptic clefts during neuronal excitation. Synaptic Zn and Cu regulate neuronal excitability, maintain calcium (Ca) homeostasis, and play central roles in memory formation. However, in pathological conditions such as transient global ischemia, excess Zn is secreted to synaptic clefts, which causes neuronal death and can eventually trigger the pathogenesis of a vascular type of senile dementia. We have previously investigated the characteristics of Zn-induced neurotoxicity and have demonstrated that low concentrations of Cu can exacerbate Zn neurotoxicity. Furthermore, during our pharmacological approaches to clarify the molecular pathways of Cu-enhanced Zn-induced neurotoxicity, we have revealed the involvement of Ca homeostasis disruption. In the present review, we discuss the roles of Zn and Cu in the synapse, as well as the crosstalk between Zn, Cu, and Ca, which our study along with other recent studies suggest may underlie the pathogenesis of vascular-type senile dementia.
  • Saho Yuzawa, Motonari Nakashio, Suzuna Ichimura, Mikako Shimoda, Ayaka Nakashima, Yuka Marukawa-Hashimoto, Yusuke Kawano, Kengo Suzuki, Kenichi Yoshitomi, Masahiro Kawahara, Ken-Ichiro Tanaka
    Cells 13(3) 2024年1月25日  査読有り最終著者責任著者
    Neuronal cell death is a key mechanism involved in the development and exacerbation of Parkinson's disease (PD). The excessive production of reactive oxygen species (ROS) is a major cause leading to neuronal death; therefore, compounds that prevent oxidative stress-dependent neuronal death may be promising as a preventive method for PD. Ergothioneine is a natural amino acid with antioxidant properties, and its protective functions in the body are attracting attention. However, there has been no investigation into the protective functions of ergothioneine using in vivo and in vitro PD models. Thus, in this study, we analyzed the efficacy of ergothioneine against 6-hydroxydopamine (6-OHDA)-dependent neuronal cell death using immortalized hypothalamic neurons (GT1-7 cells). First, we found that ergothioneine prevents 6-OHDA-dependent neuronal cell death by suppressing ROS overproduction in GT1-7 cells. The cytoprotective effect of ergothioneine was partially abolished by verapamil, an inhibitor of OCTN1, which is involved in ergothioneine uptake. Furthermore, ergothioneine-rich Rice-koji (Ergo-koji) showed cytoprotective and antioxidant effects similar to those of ergothioneine. Taken together, these results suggest that ergothioneine or foods containing ergothioneine may be an effective method for preventing the development and progression of PD.
  • Tsutomu Ishihara, Ken-Ichiro Tanaka, Ayaka Takafuji, Keita Miura, Tohru Mizushima
    International journal of molecular sciences 24(12) 2023年6月12日  査読有り責任著者
    As overproduction of reactive oxygen species (ROS) causes various diseases, antioxidants that scavenge ROS, or inhibitors that suppress excessive ROS generation, can be used as therapeutic agents. From a library of approved drugs, we screened compounds that reduced superoxide anions produced by pyocyanin-stimulated leukemia cells and identified benzbromarone. Further investigation of several of its analogues showed that benziodarone possessed the highest activity in reducing superoxide anions without causing cytotoxicity. In contrast, in a cell-free assay, benziodarone induced only a minimal decrease in superoxide anion levels generated by xanthine oxidase. These results suggest that benziodarone is an inhibitor of NADPH oxidases in the plasma membrane but is not a superoxide anion scavenger. We investigated the preventive effect of benziodarone on lipopolysaccharide (LPS)-induced murine lung injury as a model of acute respiratory distress syndrome (ARDS). Intratracheal administration of benziodarone attenuated tissue damage and inflammation via its ROS-reducing activity. These results indicate the potential application of benziodarone as a therapeutic agent against diseases caused by ROS overproduction.
  • Okina Sakakibara, Mikako Shimoda, Gaku Yamamoto, Youichirou Higashi, Mayumi Ikeda-Imafuku, Yu Ishima, Masahiro Kawahara, Ken-Ichiro Tanaka
    International journal of molecular sciences 24(11) 2023年6月5日  査読有り最終著者責任著者
    Parkinson's disease (PD) is a neurodegenerative disorder caused by oxidative stress-dependent loss of dopaminergic neurons in the substantia nigra and elevated microglial inflammatory responses. Recent studies show that cell loss also occurs in the hypothalamus in PD. However, effective treatments for the disorder are lacking. Thioredoxin is the major protein disulfide reductase in vivo. We previously synthesized an albumin-thioredoxin fusion protein (Alb-Trx), which has a longer plasma half-life than thioredoxin, and reported its effectiveness in the treatment of respiratory and renal diseases. Moreover, we reported that the fusion protein inhibits trace metal-dependent cell death in cerebrovascular dementia. Here, we investigated the effectiveness of Alb-Trx against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. Alb-Trx significantly inhibited 6-OHDA-induced neuronal cell death and the integrated stress response. Alb-Trx also markedly inhibited 6-OHDA-induced reactive oxygen species (ROS) production, at a concentration similar to that inhibiting cell death. Exposure to 6-OHDA perturbed the mitogen-activated protein kinase pathway, with increased phosphorylated Jun N-terminal kinase and decreased phosphorylated extracellular signal-regulated kinase levels. Alb-Trx pretreatment ameliorated these changes. Furthermore, Alb-Trx suppressed 6-OHDA-induced neuroinflammatory responses by inhibiting NF-κB activation. These findings suggest that Alb-Trx reduces neuronal cell death and neuroinflammatory responses by ameliorating ROS-mediated disruptions in intracellular signaling pathways. Thus, Alb-Trx may have potential as a novel therapeutic agent for PD.
  • Masahiro Kawahara, Midori Kato-Negishi, Ken-Ichiro Tanaka
    Nutrients 15(9) 2023年4月25日  査読有り最終著者
    Trace elements such as iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn) are absorbed from food via the gastrointestinal tract, transported into the brain, and play central roles in normal brain functions. An excess of these trace elements often produces reactive oxygen species and damages the brain. Moreover, increasing evidence suggests that the dyshomeostasis of these metals is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, prion diseases, and Lewy body diseases. The disease-related amyloidogenic proteins can regulate metal homeostasis at the synapses, and thus loss of the protective functions of these amyloidogenic proteins causes neurodegeneration. Meanwhile, metal-induced conformational changes of the amyloidogenic proteins contribute to enhancing their neurotoxicity. Moreover, excess Zn and Cu play central roles in the pathogenesis of vascular-type senile dementia. Here, we present an overview of the intake, absorption, and transport of four essential elements (Fe, Zn, Cu, Mn) and one non-essential element (aluminum: Al) in food and their connections with the pathogenesis of neurodegenerative diseases based on metal-protein, and metal-metal cross-talk.

MISC

 137

書籍等出版物

 1

講演・口頭発表等

 86

所属学協会

 8

共同研究・競争的資金等の研究課題

 16

社会貢献活動

 5

教育内容・方法の工夫

 3
  • 件名
    PowerPoint・空欄入りプリント使用した講義の実施
    年月日(From)
    2009/04
  • 件名
    質問カードの配布とそれに対する解説の実施
    年月日(From)
    2009/04
  • 件名
    前回講義に関するミニテストの実施
    年月日(From)
    2013/04

資格・免許

 1
  • 件名
    薬剤師免許
    年月日
    2003/09