Toshiyuki Matsunaga


Affiliation: Gifu Pharmaceutical University
Country: Japan


  1. Morikawa Y, Shibata A, Sasajima Y, Suenami K, Sato K, Takekoshi Y, et al. Sibutramine facilitates apoptosis and contraction of aortic smooth muscle cells through elevating production of reactive oxygen species. Eur J Pharmacol. 2018;841:113-121 pubmed publisher
  2. Takashina Y, Manabe A, Hasegawa H, Matsunaga T, Endo S, Ikari A. Sodium Citrate Increases Expression and Flux of Mg2+ Transport Carriers Mediated by Activation of MEK/ERK/c-Fos Pathway in Renal Tubular Epithelial Cells. Nutrients. 2018;10: pubmed publisher
    ..These results suggest that SC increases TRPM6 expression and Mg2+ influx mediated by the activation of NADPH oxidase and an EGFR/ERK/c-Fos pathway in the renal tubules. ..
  3. Matsunaga T, Shinoda Y, Inoue Y, Shimizu Y, Haga M, Endo S, et al. Aldo-keto reductase 1C15 as a quinone reductase in rat endothelial cell: its involvement in redox cycling of 9,10-phenanthrenequinone. Free Radic Res. 2011;45:848-57 pubmed publisher
    ..9,10-PQ also provoked the AKR1C15 up-regulation, which sensitized against the quinone toxicity. These results suggest the presence of a negative feedback loop exacerbating the quinone toxicity in rat endothelial cells. ..
  4. Morikawa Y, Shibata A, Okumura N, Ikari A, Sasajima Y, Suenami K, et al. Sibutramine provokes apoptosis of aortic endothelial cells through altered production of reactive oxygen and nitrogen species. Toxicol Appl Pharmacol. 2017;314:1-11 pubmed publisher
    ..This study also suggests an inverse relationship between sibutramine cytotoxicity and CYP3A4-mediated metabolism into the N-desmethyl metabolites. ..
  5. Matsunaga T, Suzuki A, Kezuka C, Okumura N, Iguchi K, Inoue I, et al. Aldo-keto reductase 1B10 promotes development of cisplatin resistance in gastrointestinal cancer cells through down-regulating peroxisome proliferator-activated receptor-?-dependent mechanism. Chem Biol Interact. 2016;256:142-53 pubmed publisher
    ..These results suggest that combined treatment with the AKR1B10 inhibitor and PPAR? ligand is an effective adjuvant therapy for overcoming CDDP resistance of gastrointestinal cancer cells. ..
  6. Endo S, Noda M, Ikari A, Tatematsu K, El Kabbani O, Hara A, et al. Characterization of hamster NAD+-dependent 3(17)β-hydroxysteroid dehydrogenase belonging to the aldo-keto reductase 1C subfamily. J Biochem. 2015;158:425-34 pubmed publisher
    ..The mutation of Val54Ala, but not Cys310Phe, significantly impaired this activity, suggesting that Val54 plays a critical role in recognition of the steroidal substrate. ..
  7. Matsunaga T, Kamase K, Takasawa H, Yamaji Y, Endo S, El Kabbani O, et al. Facilitation of 9,10-phenanthrenequinone-elicited neuroblastoma cell apoptosis by NAD(P)H:quinone oxidoreductase 1. Chem Biol Interact. 2018;279:10-20 pubmed publisher
    ..Taken together, PQ exposure produces large amounts of ROS in neuroblastoma cells via NQO1 up-regulation and resultant acceleration of its redox-cycling, followed by activation of the ROS-dependent apoptotic mechanism. ..
  8. Matsunaga T, Morikawa Y, Kamata K, Shibata A, Miyazono H, Sasajima Y, et al. ?-Pyrrolidinononanophenone provokes apoptosis of neuronal cells through alterations in antioxidant properties. Toxicology. 2017;386:93-102 pubmed publisher
  9. Sonoki H, Sato T, Endo S, Matsunaga T, Yamaguchi M, Yamazaki Y, et al. Quercetin Decreases Claudin-2 Expression Mediated by Up-Regulation of microRNA miR-16 in Lung Adenocarcinoma A549 Cells. Nutrients. 2015;7:4578-92 pubmed publisher
    ..These results suggest that quercetin decreases claudin-2 expression mediated by up-regulation of miR-16 expression and instability of claudin-2 mRNA in lung adenocarcinoma cells. ..

More Information


  1. Morikawa Y, Kezuka C, Endo S, Ikari A, Soda M, Yamamura K, et al. Acquisition of doxorubicin resistance facilitates migrating and invasive potentials of gastric cancer MKN45 cells through up-regulating aldo-keto reductase 1B10. Chem Biol Interact. 2015;230:30-9 pubmed publisher
    ..These results suggest that AKR1B10 is a DOX-resistance gene in the gastric cancer cells, and is responsible for elevating the migrating and invasive potentials of the cells through induction of MMP2. ..
  2. Matsunaga T, Hojo A, Yamane Y, Endo S, El Kabbani O, Hara A. Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers. Chem Biol Interact. 2013;202:234-42 pubmed publisher
    ..Collectively, these results suggest the involvement of up-regulated AKR1C1, AKR1C3 and proteasome in CDDP resistance of colon cancers and support a chemotherapeutic role for their inhibitors. ..
  3. request reprint
    Matsunaga T, Hosogai M, Arakaki M, Endo S, El Kabbani O, Hara A. 9,10-phenanthrenequinone induces monocytic differentiation of U937 cells through regulating expression of aldo-keto reductase 1C3. Biol Pharm Bull. 2012;35:1598-602 pubmed
    ..These results suggest that ROS formation during 9,10-PQ treatment acutely leads to apoptosis of U937 cells and the initiation of monocytic differentiation, which proceeds after the provisional overexpression of AKR1C3. ..
  4. Matsunaga T, Endo S, Maeda S, Ishikura S, Tajima K, Tanaka N, et al. Characterization of human DHRS4: an inducible short-chain dehydrogenase/reductase enzyme with 3beta-hydroxysteroid dehydrogenase activity. Arch Biochem Biophys. 2008;477:339-47 pubmed publisher
    ..The results suggest a novel mechanism of cold inactivation and role of the inducible human DHRS4 in 3beta-hydroxysteroid synthesis and xenobiotic carbonyl metabolism. ..
  5. Sonoki H, Tanimae A, Endo S, Matsunaga T, Furuta T, Ichihara K, et al. Kaempherol and Luteolin Decrease Claudin-2 Expression Mediated by Inhibition of STAT3 in Lung Adenocarcinoma A549 Cells. Nutrients. 2017;9: pubmed publisher
    ..The intake of foods and nutrients rich in these flavonoids may prevent lung adenocarcinoma development. ..
  6. Matsunaga T, Yamane Y, Iida K, Endo S, Banno Y, El Kabbani O, et al. Involvement of the aldo-keto reductase, AKR1B10, in mitomycin-c resistance through reactive oxygen species-dependent mechanisms. Anticancer Drugs. 2011;22:402-8 pubmed publisher
    ..These results suggest a role of AKR1B10 in the development of MMC resistance, which may be mediated by its ability to detoxify cytotoxic aldehydes including 4-hydroxy-2-nonenal. ..
  7. Matsunaga T, Shinoda Y, Inoue Y, Endo S, El Kabbani O, Hara A. Protective effect of rat aldo-keto reductase (AKR1C15) on endothelial cell damage elicited by 4-hydroxy-2-nonenal. Chem Biol Interact. 2011;191:364-70 pubmed publisher
    ..Collectively, these data indicate an anti-atherogenic function of AKR1C15 through the protection of endothelial cells from damage elicited by toxic lipids such as HNE. ..
  8. Matsunaga T, Arakaki M, Kamiya T, Endo S, El Kabbani O, Hara A. Involvement of an aldo-keto reductase (AKR1C3) in redox cycling of 9,10-phenanthrenequinone leading to apoptosis in human endothelial cells. Chem Biol Interact. 2009;181:52-60 pubmed publisher
    ..These results suggest that AKR1C3 is a key enzyme in the initial step of 9,10-PQ-induced cytotoxicity in HAECs. ..