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.
研究課題 Research Objectives
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
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
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
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
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).
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).
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).
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)
