Field of Study
Bioinformatics, Biology, Toxicology, Nutrition
Keywords
Illicit drug, Toxicant, Chemoresistance, Lipid nutrition
Lab URL
https://www.gifu-pu.ac.jp/lab/seitai-joho/
薬物や脂質による生体情報を元に、未知の生理現象の解明を目指す
Elucidate the novel physiological phenomena based on the bioinformatics from drugs or lipids.
  • 教授(兼務) 松永 俊之 Professor Matsunaga Toshiyuki Ph.D. matsunagat
  • 講師 立松 憲次郎 Associate Professor Tatematsu Kenjiro Ph.D. tateken

研究テーマ Research Subjects

1 . 有害物質による健康被害の分子機構の解明:これまでに危険ドラッグや覚せい剤、やせ薬等の違法薬物の乱用、有毒植物の喫食や大気汚染物質への曝露による健康被害事例が多数報告されている。いくつかの違法薬物や大気汚染物質は活性酸素種等の産生亢進を介して脳神経系、循環器系や呼吸器系組織に対して重篤な障害を引き起こす。本研究室では、それら有害物質の構造毒性相関解析やメタボローム解析等を駆使して健康被害の分子機構の解明研究を行っている。

2 . 抗がん耐性化を克服する新規補助化学療法の開発:継続的な抗がん剤投与は抗がん剤に対する感受性の低下(抗がん剤耐性化)が起こるため、本耐性化を抑制する画期的な補助化学療法の開発が切望されている。本研究室では、抗がん剤等の生体異物代謝酵素、薬物輸送体タンパク質やプロテアソームを標的とした新規補助化学療法の開発研究に取り組んでいる。

3 . 脂質栄養による生活習慣病予防効果の検討:必須脂肪酸の n- 6 /n- 3 比を下げる栄養指導は各種疾患に対して予防・治療効果があり、一部の脂肪酸は医薬品としても使用されている。しかし、n- 6 /n- 3 以外の脂肪酸、各種ステロール類、脂溶性の微量成分については、長期摂取の検討は多くない。本研究室では、脂質栄養と疾患にまつわる種々の未解決のテーマについて、実験動物に対する油脂の長期投与の系を用いて取り組んでいる。これらを解決することで、生活習慣病の予防に対する脂質栄養の指針確立に貢献したいと考えている。

1 . Elucidation of molecular mechanisms underlying health hazards due to exposure to toxic substances. Previously, there have been lots of reports that pose serious health hazards associated with abuse of illicit drugs, such as designer drugs, psychostimulants and anti-obesity agents, intake of toxic plants and inhalation of all pollutants. Exposure to some illicit drugs or air pollutants elicits severe injuries to cranial nerve and cardiovascular systems and respiratory tract through elevating production of reactive oxygen species. We aim to elucidate the detailed molecular mechanisms of major health hazards arising from exposure to their toxic substances by performing the structure-toxic relationship and metabolome analyses.

2 . Development of novel adjuvant therapies to overcome chemo-resistance in cancer cells. Continuous administration of anticancer drugs provokes the hyposensitivity, so-called chemo-resistance, of cancer cells and, therefore, development of effective adjuvants that alleviate the gain of chemo-resistance is desired. In this laboratory, we investigate to develop novel adjuvant therapies targeted to xenobiotic-metabolizing enzymes, drug transporter proteins and proteasomal proteolysis.

3 . Investigation into preventive effect of lipid nutrition on lifestyle disease. Nutritional guidance to lower the n-6/ n-3 ratio of essential fatty acids has preventive and therapeutic effects on various diseases, and some essential fatty acids are also used as medicine. However, there are not many studies on long-term intake of fatty acids other than n-6/n-3, various sterols, and fat-soluble minor component. In this laboratory, we are addressing various unresolved topics related to lipid nutrition and diseases using a system of long-term administration of fats and oils to experimental animals. By solving these problems, we hope to contribute to the establishment of guidelines for lipid nutrition for the prevention of lifestyle-related diseases.

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研究課題 Research Objectives

  1. 違法薬物や大気汚染物質による脳神経損傷機序の解明
    Elucidation of mechanisms underlying cranial nerve injury elicited by illicit drugs and air pollutants
  2. 食中毒の病因物質の同定と発症機序に関する研究
    Studies on identification of causal factors and pathogenic mechanisms of food poisoning
  3. 抗がん耐性化関連タンパク質を標的とする新規補助化学療法剤の探索
    Exploration of novel adjuvants to targeted to proteins related with chemo-resistance of cancer cells
  4. 脂質栄養による生活習慣病予防効果の検討
    Investigation into preventive effect of lipid nutrition on lifestyle disease

最近の研究成果 Research Results

  1. Sakai Y., Taguchi M., Morikawa Y., Suenami K., Yanase E., Takayama T., Ikari A., Matsunaga T., Lowering of brain endothelial cell barrier function by exposure to 4'-iodo-a-pyrrolidinononanophenone. Chem. Biol. Interact., 364, 110052 (2022).

  2. Sakai Y., Taguchi M., Morikawa Y., Miyazono H., Suenami K., Ochiai Y., Yanase E., Takayama T., Ikari A., Matsunaga T., Apoptotic mechanism in human brain microvascular endothelial cells triggered by 4'-iodo-a-pyrrolidinononanophenone: Contribution of decrease in antioxidant properties. Toxicol. Lett., 355, 127-140 (2022).

  3. Kobayashi M., Yonezawa A., Takasawa H., Nagao Y., Iguchi K., Endo S., Ikari A., Matsunaga T., Development of cisplatin resistance in breast cancer MCF7 cells by up-regulating aldo-keto reductase 1C3 expression, glutathione synthesis and proteasomal proteolysis. J. Biochem., 171, 97-108 (2022).

  4. Nishikawa M, Ohara N, Naito Y, Saito Y, Amma C, Tatematsu K, Baoyindugurong J, Miyazawa D, Hashimoto Y, Okuyama H. Rapeseed (canola) oil aggravates metabolic syndrome-like conditions in male but not in female stroke-prone spontaneously hypertensive rats (SHRSP). Toxicol. Rep. 9, 256-268 (2022)