広島大学 大学院統合生命科学研究科 生命医科学プログラム 生体機能化学研究室

2024年

 

1. Kono M, Takaishi M, Okuda T, Fujihara M, Noguchi S, Ishihara Y*. A simple air-liquid interface exposure system for exposing cultured human 3D epidermis and cornea to PM2.5 collected through cyclonic separation. J Toxicol Sci. 49(2):61-68, 2024.
培養細胞に対してPM2.5を気相曝露できるチャンバーシステムを開発しました。曝露するPM2.5の濃度を自由に変えれる点が最大の長所です。

 

2. Kajino M*, Kayaba S*, Ishihara Y*, Iwamoto Y, Okuda T, Okochi H. Numerical simulation of IL-8-based relative inflammation potentials of aerosol particles from vehicle exhaust and non-exhaust emission sources in Japan. Atmos Environ X. 21:100237, 2024.
気象研梶野先生の研究に加えてもらっています。環境モデルと毒性学を融合させた毒性モデリングという新しい分野の開拓を目指しており、この論文では排気粒子、非排気粒子の炎症リスクをマッピングしました。

 

3. Namba K, Tominaga T, Ishihara Y*. Decreases in the number of microglia and neural circuit dysfunction elicited by developmental exposure to neonicotinoid pesticides in mice. Environ Toxicol. In Press.
発達期にイミダクロプリド（ネオニコチノイド系農薬）を曝露すると、ミクログリア数が減少し、神経回路機能が障害されて成長後の行動異常が生じることを明らかにしました。難波さんの研究の集大成です。

 

4. 石原 康宏，岩本 洋子，奥田 知明，大河内 博，鍋谷 悠，河野 まおり. 太陽光劣化繊維状ポリエチレンテレフタラートの呼吸器影響評価. 大気環境学会誌 59巻1号 A44 2024年.

 

5. 大河内 博，谷 悠人，小野塚 洋介，王 一澤，速水 洋，竹内 政樹，反町 篤行，藤井 佑介，竹中 規訓，宮崎 あかね，須永 奈都，羽山 伸一，徳長 ゆり香，山口 高志，勝見 尚也，松木 篤，池盛 文数，梶野 瑞王，足立 光司，石原 康宏，岩本 洋子，新居田 恭弘. AMΦプロジェクト: プラスチック大気汚染はどこまで解明されたのか？大気環境学会誌 59巻1号 A32 2024年.

 

6. 反町 篤行，愛甲 竜也，王 森，貞弘 悠希，増田 裕介，田中 厚資，鈴木 剛，大河内 博，石原 康宏. 汎用プラスチックから合成したモデルプラスチック粒子.大気環境学会誌 59巻1号 A35 2024年.

 

7. 梶野 瑞王，足立 光司，大河内 博，石原 康宏，茅場 聡子，阪口 悠宇. マイクロプラスチックの3 次元モデル予測. 大気環境学会誌 59巻1号 A37 2024年.

 

 

 

2023年

 

1. Kono M, Okuda T, Ishihara N, Hagino H, Tani Y, Okochi H, Tokoro C, Takaishi M, Ikeda H, Ishihara Y*. Chemokine expression in human 3-dimensional cultured epidermis exposed to PM2.5 collected by cyclonic separation. Toxicol Res. 39(1):1-13, 2023.
皮膚にPM2.5を曝露すると、ケモカインの発現が上昇し、好中球性の炎症が生じることを示しました。

 

2. Akizuki K, Shimoda N, Ozaki H, Yamazaki T, Hirano T, Ishihara Y, Sueyoshi N, Kameshita I, Murai T, Ishida A*. CaMK phosphatase (CaMKP/POPX2/PPM1F) inhibitors suppress the migration of human breast cancer MDA-MB-231 cells with loss of polarized morphology. Biochem Biophys Res Commun. 639:1-8, 2023.

 

3. Tanaka M, Okuda T, Itoh K, Ishihara N, Oguro A, Fujii-Kuriyama Y, Nabetani Y, Yamamoto M, Vogel CFA, Ishihara Y*. Polycyclic aromatic hydrocarbons in urban particle matter exacerbate movement disorder after ischemic stroke via potentiation of neuroinflammation. Particle Fibre Toxicol. 20:6 2023.
PM2.5を曝露するとミクログリアが活性化し、脳梗塞の予後が悪化することを明らかにしました。博士号を取得した田中さんの渾身の作です。

 

4. Tsuji M*, Koriyama C, Ishihara Y, Isse T, Ishitsuka T, Hasegawa W, Goto M, Tanaka R, Kakiuchi N, Hori H, Yatera K, Kunugita N, Yamamoto M, Sakuragi T, Yasumura Y, Kono M, Kuwamura M, Kitagawa K, Ueno S. Associations between welding fume exposure and neurological function in Japanese male welders and non-welders. J Occup Health. 65:e12393, 2023.

 

5. Halmouch YE, Ibrahim HAH, Dofdaa NM, Mabrouk MEM, El-Metwally MM, Nehira T, Ferji K, Ishihara Y, Matsuo K*, Ibrahim MIA*. Complementary spectroscopy studies and potential activities of levan-type fructan produced by Bacillus paralicheniformis ND2. Carbohydr Polym. 311:120743, 2023.

 

6. Ishihara Y*, Itoh K. Microglial inflammatory reaction regulated by oxidative stress. J Clin Biochem Nutr. 72(1): 23-27, 2023.
酸化ストレスとミクログリア活性との関連について纏めた総説です。

 

7. Kawano S, Itoh K, Ishihara Y*. Suppressive effects of docosahexaenoic acid intake on increased seizure susceptibility after growth due to febrile seizures in infancy. Biol Pharm Bull. 46:1184-1193, 2023.
ドコサヘキサエン酸を摂取により、熱性けいれんを起こした後のけいれん感受性の上昇が抑制される（けいれんを起しにくくなる）ことを示した論文です。川野くんが脳波測定＆解析に挑戦してくれて形になりました。

 

8. Tsuji M*, Hori H, Koriyama C, Tanaka R, Isse T, Ishihara Y, Ishizuka T, Hasegawa W, Goto M, Yatera K, Kunugita N, Kuwamura M, Sakuragi T, Yasumura Y, Yamamoto M, Ueno S. The effect of mask fit test on the association between the concentration of metals in biological samples and the results of time-weighted average personal exposure: a study on Japanese male welders. J Occup Health, 65(1):e12399, 2023.

 

9. Kado SY, Bein K, Castaneda AR, Pouraryan AA, Garrity N, Ishihara Y, Rossi A, Haarmann-Stemmann T, Sweeney CA, Vogel CFA*. Regulation of IDO2 by the Aryl Hydrocarbon Receptor (AhR) in Breast Cancer. Cells 12(10):1433, 2023.

 

10. Wang Y*, Okochi H*, Tani Y, Hayami H, Minami Y, Katsumi N, Takeuchi M, Sorimachi M, Fujii Y, Kajino M, Adachi K, Ishihara Y, Iwamoto Y, Niida Y. Airborne hydrophilic microplastics in cloud water at high altitudes and their role in cloud formation. Environ Chem Lett. 21:3055-3062, 2023.

 

11. Oguro A*, Fujiyama T, Ishihara Y, Kataoka C, Yamamoto M, Eto K, Komohara Y, Imaoka S, Sakuragi T, Tsuji M, Shibata E, Kotake Y, Yamazaki T. Maternal DHA intake in mice increased DHA metabolites in the pup brain and ameliorated MeHg-induced behavioral disorder. J Lipid Res. 64(11):100458, 2023.

 

12. 石原 康宏、河野 まおり、大河内 博、奥田 知明. 道路粉塵の健康影響評価：都市型PM2.5との比較. 大気環境学会誌 58巻1号 A44 2023年.

 

13. 梶野 瑞王、足立 光司、大河内 博、石原 康宏、茅場 聡子、阪口 悠宇. マイクロプラスチックの3次元モデル予測に向けて. 大気環境学会誌. 58巻1号 A49 2023年.

 

14. 大河内 博、谷 悠人、吉田 昇永、王 一澤、趙 鶴立、小野塚 洋介、藤川 真智子、速水 洋、竹内 政樹、樫本 真央、反町 篤行、藤井 佑介、竹中 規訓、北野 洸太朗、宮崎 あかね、須永 奈都、羽山 伸一、徳長 ゆり香、山口 高志、勝見 尚也、松木 篤、池盛 文数、梶野 瑞王、足立 光司、石原 康宏、岩本 洋子、新居田 恭弘、小林 華栄、浦山 憲雄. 大気中マイクロプラスチックの実態解明と健康影響評価. 大気環境学会誌 58巻1号 A29 2023年.

 

15. 和田 百合花、河野 まおり、鍋谷 悠、石原 康宏. 大気中マイクロプラスチック毒性研究の現状と課題. エアロゾル研究 38巻3号 P. 181-186 2023年.

 

16. 大河内 博、谷 悠人、小野塚 洋介、王 一澤、速水 洋、竹内 政樹、反町 篤行、藤井 佑介、竹中 規訓、宮崎 あかね、須永 奈都、羽山 伸一、徳長 ゆり香、山口 高志、勝見 尚也、松木 篤、池盛 文数、梶野 瑞王、足立 光司、石原 康宏、岩本 洋子、新居田 恭弘. プラスチック大気汚染の現状と課題. エアロゾル研究 38巻3号 P. 145-159 2023年.

 

 

 

2022年

 

1. Ishihara Y, Kado K, He Y, Pouraryan AA, Urban A, Bein KJ, Haarmann-Stemmann T, Sweeney C, Vogel CF*. Aryl hydrocarbon Receptor signaling synergizes with TLR/NF-kB-signaling for induction of IL-22 through canonical and non-canonical AhR pathways. Front Toxicol. 3:787360, 2022.
AhRシグナルとTLRシグナルとのクロストークにより、IL-22の発現が劇的に上昇することを明らかにしました。

 

2. Chen J, Minabe S, Munetomo A, Magata F, Sato M, Nakamura S, Hirabayashi M, Ishihara Y, Yamazaki T, Uenoyama Y, Tsukamura H, Matsuda F*. Kiss1-dependent and independent release of luteinizing hormone and testosterone in perinatal male rats. Endocrine J. doi: 10.1507/endocrj.EJ21-0620.

 

3. Ishihara N, Okuda T, Hagino H, Oguro A, Tani Y, Okochi H, Tokoro C, Fujii-Kuriyama Y, Itoh K, Vogel CFA, Ishihara Y*. Involvement of polycyclic aromatic hydrocarbons and endotoxin in macrophage expression of interleukin-33 induced by exposure to particulate matter. J Toxicol Sci. 47:201-210, 2022.
PM2.5に含まれる多環芳香族炭化水素とエンドトキシンがIL-33の発現を誘導することを示した論文です。

 

4. Matsuo T, Komori R, Nakatani M, Ochi S, Yokota-Nakatsuma A, Ishihara Y, Itoh K*. Levetiracetam suppresses infiltration of neutrophils and monocytes and downregulates many inflammatory cytokines during epileptogenesis in pilocarpine-induced status epilepticus mice. Int J Mol Sci. 23(14):7671, 2022.

 

5. Komori R, Matsuo T, Yokota-Nakatsuma A, Hashimoto R, Kubo S, Kozawa C, Kono T, Ishihara Y, Itoh K*. Regulation of inflammation-related genes through Fosl1 suppression in a levetiracetam-treated pilocarpine-induced status epilepticus mouse model. Int J Mol Sci. 23(14):7608, 2022.

 

6. Kono M, Okuda T, Takaishi M, Ikeda H, Ishihara N, Ishihara Y*. Leaf extracts from the Camellia sinensis and the Argania spinosa suppressed oxidative stress and chemokine release in human 3-dimensional cultured epidermis exposed to PM2.5 collected with cyclonic separation. Fundam Toxicol Sci. 9:117-122, 2022.
PM2.5の皮膚への作用を軽減する植物エキスをスクリーニングし、候補エキスを2つ（お茶とアルガン）挙げています。

 

7. Ishihara Y*, Honda T, Ishihara N, Namba K, Taketoshi M, Tominaga Y, Tsuji M, Vogel CFA, Yamazaki T, Itoh K, Tominaga T. A CCR5 antagonist, maraviroc, alleviates neural circuit dysfunction and behavioural disorders induced by prenatal valproate exposure. J Neuroinflam. 19:195, 2022.
胎児期のバルプロ酸曝露により生じる発達神経毒性において、ミクログリア由来のケモカインCCL3が神経回路機能を障害することを明らかにした論文です。

 

8. Fujikawa A, Ishihara Y*, Ohta E, Nehira T*, Omura H, Uy MM, Ohta S*. Fluorescent Benzoxazines with Neuroprotective Activity from the Olive Weevil, Pimelocerus perforates. J Nat Prod. 85:2740?2745, 2022.

 

9. 石原 康宏. 活性酸素. 人間の許容限界事典（分担執筆）朝倉書店 2022年.

 

 

2021年

 

1. Oguro A*, Ishihara Y, Siswanto FM, Yamazaki T, Ishida A, Imaishi H, Imaoka S, Contribution of DHA diols (19,20-DHDP) produced by cytochrome P450s and soluble epoxide hydrolase to the beneficial effects of DHA supplementation in the brains of rotenone-induced rat models of Parkinson’s disease. Biochim Biophys Acta Mol Cell Biol Lipids, 1866:158858, 2021.

 

2. Vogel CFA*, Lazennec G, Kado SY, Dahlem C, He Y, Castaneda A, Ishihara Y, Vogeley C, Rossi A, Haarmann-Stemmann T, Jugan JA, Mori H, Borowsky AD, La Merrill MA, Sweeney C. Targeting the aryl hydrocarbon receptor signaling pathway in breast cancer development. Front Immunol. 12:625346, 2021.

 

3. Oguro A*, Fujita K, Ishihara Y, Yamamoto M, Yamazaki T. DHA and its metabolites have a protective role against methylmercury-induced neurotoxicity in mouse primary neuron and SH-SY5Y cells. Int J Mol Sci. 22(6):3213, 2021.

 

4. Tanaka M, Fujikawa M, Oguro A, Itoh K, Vogel CFA, Ishihara Y*. Involvement of the microglial aryl hydrocarbon receptor in neuroinflammation and vasogenic edema after ischemic stroke. Cells. 10(4):718, 2021.

 

5. Oguro A*, Sugitani A, Kobayashi Y, Sakuma R, and Imaoka S*. Bisphenol A stabilizes Nrf2 via Ca2+ influx by direct activation of the IP3 receptor. J Toxicol Sci., 45(12):783-794, 2021.

 

6. Kobayashi Y, Oguro A, Hirata Y, Imaoka S*. The regulation of Hypoxia-Inducible Factor-1 (HIF-1alpha) expression by Protein Disulfide Isomerase (PDI). PLoS One. 16(2):e0246531, 2021.

 

7. Kobayashi Y, Oguro A, Imaoka S*. Feedback of hypoxia-inducible factor-1alpha (HIF-1alpha) transcriptional activity via redox factor-1 (Ref-1) induction by reactive oxygen species (ROS). Free Radic Res. 55:154, 2021.

 

8. Kawano S, Itoh K, Ishihara Y*. Maternal intake of docosahexaenoic acid decreased febrile seizure sensitivity by increasing estrogen synthesis in offspring. Epilepsy Behav. 121:108038, 2021.

 

9. Siswanto FM, Oguro A, Imaoka S*. Sp1 is a substrate of Keap1 and regulates the activity of CRL4A WDR23 ubiquitin ligase toward Nrf2. J Biol Chem. 296:100704, 2021.

 

10. Ohta S*, Takeda M, Ohta E, Nehira T, Omura H, Uy MM, Ishihara Y*. Janohigenins: Long-chain anacardic acid derivatives with neuroprotective activity from Ophiopogon japonicus seeds. Phytochemistry 191:112904, 2021.

 

11. Niidome K, Taniguchi R, Yamazaki T, Tsuji M, Itoh K, Ishihara Y*. FosL1 Is a Novel Target of Levetiracetam for Suppressing the Microglial Inflammatory Reaction. Int J Mol Sci. 22(20):10962, 2021.

 

 

2020年

 

1. Siswanto FM, Oguro A, Arase S, Imaoka S*. WDR23 regulates the expression of Nrf2-driven drug-metabolizing enzymes. Drug Metab Pharmacokinet. 35:441-455, 2020

 

2. Kobayashi Y, Oguro A, Yagi E, Mitani A, Kudoh SN, Imaoka S*. Bisphenol A and rotenone induce S-nitrosylation of protein disulfide isomerase (PDI) and inhibit neurite outgrowth of primary cultured cells of the rat hippocampus and PC12 cells. J Toxicol Sci., 45(12), 783-794, 2020

 

3. Ishii M, Senju A, Oguro A, Shimono M, Araki S, Kusuhara K, Itoh K, Tsuji M, Ishihara Y*. Measurement of the estradiol concentration in cerebrospinal fluid from infants and its correlation with serum estradiol and exosomal microRNA-126-5p. Biol Pharm Bull. 43(12):1966-1968, 2020.

 

4. Ohta S*, Oshimo S, Ohta E, Nehira T, Omura H, Uy M, Ishihara Y*. Asaroidoxazines from the Roots of Asarum asaroides Induce Apoptosis in Human Neuroblastoma Cells. J Nat Prod. 83(10):3050-3057, 2020.

 

2019年

 

1. Ishihara Y*, Itoh K, Oguro A, Chiba Y, Ueno M, Tsuji M, Vogel CFA, Yamazaki T. Neuroprotective activation of astrocytes by methylmercury exposure in the inferior colliculus. Sci Rep. 9:13899 (2019).

 

2. Oguro A*, and Imaoka S. Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-beta-dependent nuclear cargo transport. Sci Rep. 9(1):15296 (2019).

 

3. Ishihara Y*, Sakurai H, Oguro A, Tsuji M, Vogel CFA, Yamazaki T. Retinoid X receptor-mediated neuroprotection via CYP19 upregulation and subsequent increases in estradiol synthesis. J Steroid Biochem Mol Biol. 193:105421, 2019.

 

4. Itoh K, Taniguchi R, Oguro A, Vogel CFA, Yamazaki T, Ishihara Y*. Suppressive effects of levetiracetam on neuroinflammation and phagocytic microglia: a comparative study of levetiracetam, valproate and carbamazepine. Neurosci Lett. 708:134363, 2019.

 

5. Tsuji M*, Koriyama C, Kanatani K, Onishi K, Bamai YA, Yamamoto-Hanada K, Senjyu A, Araki S, Shibata E, Morokuma S, Sanefuji M, Yamamoto M, Ishihara Y, Kusuhara K, Tanaka R, Kawamoto T, Japan Environment & Children’s Study Group. Associations between metal levels in whole blood and IgE concentrations in pregnant women, based on data from the Japan Environment and Children's Study. J Epidemiol. 29(12):478-486, 2019.

 

6. Tsuji M*, Koriyama C, Ishihara Y, Vogel CFA, Kawamoto T. Association between bisphenol A diglycidyl ether-specific IgG in serum and food sensitization in young children. Eur J Med Res. 23(1):61 (2018).

 

7. Ishihara Y*, Haarmann-Stemmannd T, Kado NY, Vogel CFA. Interleukin 33 expression induced by aryl hydrocarbon receptor in macrophages. Toxicol Sci. 170(2):404-414, 2019.

 

8. Tsuji M*, Shibata E, Askew DJ, Morokuma S, Aiko Y, Senju A, Araki S, Sanefuji M, Ishihara Y, Tanaka R, Kusuhara K, Kawamoto T and the Japan Environment and Children’s Study Group. Associations between metal concentrations in whole blood and placenta previa and placenta accreta: The Japan Environment and Children’s Study. Environ Health Prev Med. 24(1):40, 2019.

 

9. Vogel CFA*, Ishihara Y, Campbell CE, Kado SY, Nguyen-Chi A, Sweeney C, Pollet M, Haarmann-Stemmann T, Tuscano JM. A protective role of aryl hydrocarbon receptor repressor in inflammation and tumor growth. Cancers (Basel). 11(5): E589, 2019.

 

10. Ishihara Y, Kado S, Hoeper C, Harel S, Vogel CFA*. Role of NF-kB RelB in AhR-mediated ligand specific effects. Int J Mol Sci. 20(11):2652, 2019.

 

2018年

 

1. Kobayashi Y, Oguro A, Imaoka S*. Bisphenol A and Its Derivatives Induce Degradation of HIF-1alpha via the Lysosomal Pathway in Human Hepatocarcinoma Cell Line, Hep3B. Biol Pharm Bull. 41(3):374-382, 2018.

 

2. Nakamura M, Yamanaka H, Oguro A, and Imaoka S*. Bisphenol A induces Nrf2-dependent drug-metabolizing enzymes through nitrosylation of Keap1, Drug Metab Pharmacokinet, 33(4):194-202, 2018.

 

3. Oguro A, Inoue T, Kudoh SN and Imaoka S*. 14,15-epoxyeicosatrienoic acid produced by cytochrome P450s enhances neurite outgrowth of PC12 and rat hippocampal neuronal cells. Pharmacol Res Perspect, 6(5):e00428, 2018.

 

4. Ishihara Y*, Ikeda-Ishihara N, Koriyama C, Kaiuchi N, Tanaka M, Vogel CFA, Kawamoto T, Tsuji M. Determination of chemical-specific IgGs in serum by an enzyme-linked immunosorbent assay with partial peptides of human serum recentin. J Toxicol Sci. 43:25-31, 2018.

 

5. Tanaka M, Ishihara Y*, Mizuno S, Ishida A, Tsuji M, Vogel CFA, Yamazaki T, Itoh K. Progression of vasogenic edema induced by activated microglia under permanent middle cerebral artery occlusion. Biochem Biophys Res Commun. 496:582-587, 2018.

 

6. Ishihara Y*, Tsuji M, Vogel CFA. Suppressive effects of aryl-hydrocarbon receptor repressor on adipocyte differentiation in 3T3-L1 cells. Arch Biochem Biophys. 642:75-80, 2018.

 

7. Baba T, Otake H, Inoue M, Sato T, Ishihara Y, Moon JY, Tsuchiya M, Miyabayashi K, Ogawa H, Shima Y, Wang L, Yamazaki T, Suyama M, Nomura M, Choi MH, Ohkawa Y, Morohashi K*. Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids. Commun Biol. 1:18, 2018.

 

8. Tsuji M*, Ishihara Y, Isse T, Koriyama C, Yamamoto M, Kakiuchi N, Yu HS, Tanaka M, Tsuchiya T, Ohta M, Tanaka R, Kawamoto T. Evaluation of chemical-specific IgG antibodies in male workers from a urethane foam factory. Environ Health Prev Med. 23(1):24, 2018.

 

9. Tsuji M*, Shibata E, Morokuma S, Tanaka R, Senjyu A, Araki S, Sanefuji M, Koriyama C, Yamamoto M, Ishihara Y, Kusuhara K, Kawamoto T and the Japan Environment & Children’s Study Group. The association between whole blood concentrations of heavy metals in pregnant women and premature births: The Japan Environment and Children's Study (JECS). Environ Res. 166:562-569, 2018.

1. 微小粒子状物質の評価方法および抗炎症剤のスクリーニング方法
出願番号：特願2022-94692

 

2. 3次元細胞培養装置およびその利用
出願番号：特願2022-37499