社会健康薬学講座 衛生薬学部門
講座紹介
衛生薬学とは、「生を衛る」薬学であり、私たちの身の回りにある食品、飲料水、大気など、社会活動を通じて人に摂取、吸収される物質によって健康に影響が出ることを防止し、健康の維持や増進を考えていくものです。衛生薬学部門では、生体のアラキドン酸代謝反応に注目し、この反応に環境中に存在する物質がどのような影響を与えるか、この反応の破綻が健康にどのような影響を及ぼすかについて、解析を進めています。1. がん等生活習慣病、神経変性疾患、炎症性疾患とアラキドン酸代謝系の破綻との関連
アスピリンなど臨床で広く用いられる非ステロイド性抗炎症薬（NSAIDs）は、シクロオキシゲナーゼ（COX）に作用し、アラキドン酸代謝物の１つ、プロスタグランジン（PG）類の生合成を抑えることで、解熱、鎮痛、抗炎症などの作用を発揮します。さらに最近になって、NSAIDsががんやアルツハイマー病にも有効なことがわかってきました。しかし、一方でPG類は様々な生理作用をもつために、従来のNSAIDsには副作用も少なくありません。衛生薬学部門では、新たなNSAIDsの標的として、COXの上流で働くホスホリパーゼA2（PLA2）と長鎖アシルCoA合成酵素（ACSL）、下流で働くPG類最終合成酵素群に注目し、これらの酵素とがん等生活習慣病、神経変性疾患、炎症性疾患との関連について、主に遺伝子改変マウスを用い解析しています。私たちの研究は、副作用のないNSAIDsの開発につながることから、国内外の製薬企業、研究機関から注目されています。2. 環境化学物質の新たな毒性発現機構の解析
メチル水銀やフタル酸エステル類、ビスフェノールAなど、ヒトや生態系に影響を及ぼす環境化学物質の多くは脂溶性に富み、生体内の脂質代謝に影響を及ぼすと考えられるものも少なくありません。衛生薬学部門では、アラキドン酸代謝系に及ぼす環境化学物質の影響を解析することで、環境化学物質の新たな毒性発現機構を明らかにしようと考えています。3. 新奇アラキドン酸代謝系の同定と生体内機能の解析
衛生薬学部門では、炎症性刺激に伴い誘導されてくるPLA2の１つ、sPLA2-IIAの発現誘導機構を解析している過程で、この発現誘導に、これまで誰も見つけることができなかった、構造未知の生理活性脂質が関わることを見出しました。生体内には未だ同定されていない生理活性脂質がなおも存在する可能性を考え、新奇生理活性脂質の同定、構造決定、機能解析を進めています。沿革
衛生化学教室は、1964年の薬学部創設時に衛生裁判化学講座として開設され、秋谷七郎教授が初代教室主任として着任なされました。その後、1972年、生物薬学科の増設に伴い衛生裁判化学の名が衛生化学に改められ、同年から1995年まで濱田昭教授が担当されました。濱田教授は糖質を中心に研究を進め、キノコ多糖の制癌性や赤血球膜糖タンパク質の構造と生物活性との関連について多くの業績をあげられました。1995年工藤一郎教授が就任し、生体内の生理活性脂質生合成の代表的な経路であるアラキドン酸代謝、特にプロスタグランジン産生機構に関する研究が開始されました。臨床医学の現場で広く用いられている非ステロイド性抗炎症薬の薬理作用が、プロスタグランジン産生系の酵素であるシクロオキシゲナーゼに対する阻害効果に起因することは良く知られておりますが、衛生化学教室では、シクロオキシゲナーゼの上流と下流でそれぞれ働くホスホリパーゼA2とプロスタグランジンE合成酵素を中心に研究を進めています。工藤教授はこの研究領域でめざましい業績をあげられ、その研究成果に対して2005年に日本薬学会賞を受賞されています。工藤教授はこれらの研究をさらに進めていく一方で、日本の医療をより良くするべく薬学教育にも精力を注いでおられましたが、2008年4月病気加療中のところご逝去されました。
2009年に原俊太郎教授が着任され、これまでの研究をさらに発展させ、“世界をリードする研究”を行うことを通じて、公衆衛生の増進に貢献すべく日々研究に取り組んでいます。
講座員
教員（専任）
| 役職 | 氏名 | name |
|---|---|---|
| 教授 | 原 俊太郎 | Hara Shuntaro |
| 准教授 | 桑田 浩 | Kuwata Hiroshi |
| 講師 | 依田 恵美子 | Yoda Emiko |
| 講師 | 佐々木 由香 | Sasaki Yuka |
| 助教 | 落合 翔 | Ochiai Tsubasa |
研究業績
2022年業績
Kuwata H, Tomitsuka Y, Yoda E, Hara S.
Role of ACSL4 in the chemical-induced cell death in human proximal tubule epithelial HK-2 cells.
Biosci Rep. 42:BSR20212433.
Role of ACSL4 in the chemical-induced cell death in human proximal tubule epithelial HK-2 cells.
Biosci Rep. 42:BSR20212433.
2021年業績
Ochiai T, Sasaki Y, Yokoyama C, Kuwata H, Hara S.
Absence of prostacyclin greatly relieves cyclophosphamide-induced cystitis and bladder pain in mice
FASEB J. 35:e21952.
Kurotaki A, Kuwata H,Hara S.
Substrate Specificity of Human Long-Chain Acyl-CoA Synthetase ACSL6 Variants.
Biol Pharm Bull. 44:1571-1575.
Sasaki Y, Kuwata H, Aida E, Ochiai T, Kamei D, Nakatani Y, Hara S.
Gene Deletion of Microsomal Prostaglandin E Synthase-1 Suppresses Chemically Induced Skin Carcinogenesis.
Anticancer Res. 41:1307-1314.
OchiaiT, Sasaki Y, KuwataH,NakataniY,YokoyamaC, HaraS.
Coordinated action of microsomal prostaglandin E synthase-1 and prostacyclin synthase on contact hypersensitivity.
Biochem Biophys Res Commun.546:124-129.
Sasaki Y, Kuwata H, Akatsu M, Yamakawa Y, Ochiai T, Yoda E, Nakatani Y, Yokoyama C, Hara S.
Involvement of prostacyclin synthase in high-fat-diet-induced obesity.
Prostaglandins Other Lipid Mediat. 153:106523.
Absence of prostacyclin greatly relieves cyclophosphamide-induced cystitis and bladder pain in mice
FASEB J. 35:e21952.
Kurotaki A, Kuwata H,Hara S.
Substrate Specificity of Human Long-Chain Acyl-CoA Synthetase ACSL6 Variants.
Biol Pharm Bull. 44:1571-1575.
Sasaki Y, Kuwata H, Aida E, Ochiai T, Kamei D, Nakatani Y, Hara S.
Gene Deletion of Microsomal Prostaglandin E Synthase-1 Suppresses Chemically Induced Skin Carcinogenesis.
Anticancer Res. 41:1307-1314.
OchiaiT, Sasaki Y, KuwataH,NakataniY,YokoyamaC, HaraS.
Coordinated action of microsomal prostaglandin E synthase-1 and prostacyclin synthase on contact hypersensitivity.
Biochem Biophys Res Commun.546:124-129.
Sasaki Y, Kuwata H, Akatsu M, Yamakawa Y, Ochiai T, Yoda E, Nakatani Y, Yokoyama C, Hara S.
Involvement of prostacyclin synthase in high-fat-diet-induced obesity.
Prostaglandins Other Lipid Mediat. 153:106523.
2020年業績
Yoda E, Hachisu K, Kuwata H, Nakatani Y, Hara S.
Gene Deletion of Calcium-Independent Phospholipase A2γ (iPLA2γ) Suppresses Adipogenic Differentiation of Mouse Embryonic Fibroblasts.
Biol Pharm Bull. 43:1375-1381.
Yamada N, Karasawa T, Kimura H, Watanabe S, Komada T, Kamata R, Sampilvanjil A, Ito J, Nakagawa K, Kuwata H, Hara S, Mizuta K, Sakuma Y, Sata N, Takahashi M.
Share Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure.
Cell Death Dis. 11:144.
Gene Deletion of Calcium-Independent Phospholipase A2γ (iPLA2γ) Suppresses Adipogenic Differentiation of Mouse Embryonic Fibroblasts.
Biol Pharm Bull. 43:1375-1381.
Yamada N, Karasawa T, Kimura H, Watanabe S, Komada T, Kamata R, Sampilvanjil A, Ito J, Nakagawa K, Kuwata H, Hara S, Mizuta K, Sakuma Y, Sata N, Takahashi M.
Share Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure.
Cell Death Dis. 11:144.
2019年業績
Kuwata H, Nakatani E, Shimbara-Matsubayashi S, Ishikawa F, Shibanuma M, Sasaki Y, Yoda E, Nakatani Y, Hara S.
Share Long-chain acyl-CoA synthetase 4 participates in the formation of highly unsaturated fatty acid-containing phospholipids in murine macrophages.
Biochim Biophys Acta Mol Cell Biol Lipids. 1864:1606-1618.
Hara S, Yoda E,Sasaki Y, Nakatani Y, Kuwata H.
Calcium-independent phospholipase A2γ(iPLA2γ) and its roles in cellular functions and diseases.
Biochim Biophys Acta Mol Cell Biol Lipids. 1864:861-868.
Shimbara-Matsubayashi S, Kuwata H, Tanaka N, Kato M, Hara S.
Analysis on the Substrate Specificity of Recombinant Human Acyl-CoA Synthetase ACSL4 Variants
Biol Pharm Bull. 42:850-855.
Kuwata H,Hara S.
Role of acyl-CoA synthetase ACSL4 in arachidonic acid metabolism.
Prostaglandins Other Lipid Mediat. 144:106363.
Share Long-chain acyl-CoA synthetase 4 participates in the formation of highly unsaturated fatty acid-containing phospholipids in murine macrophages.
Biochim Biophys Acta Mol Cell Biol Lipids. 1864:1606-1618.
Hara S, Yoda E,Sasaki Y, Nakatani Y, Kuwata H.
Calcium-independent phospholipase A2γ(iPLA2γ) and its roles in cellular functions and diseases.
Biochim Biophys Acta Mol Cell Biol Lipids. 1864:861-868.
Shimbara-Matsubayashi S, Kuwata H, Tanaka N, Kato M, Hara S.
Analysis on the Substrate Specificity of Recombinant Human Acyl-CoA Synthetase ACSL4 Variants
Biol Pharm Bull. 42:850-855.
Kuwata H,Hara S.
Role of acyl-CoA synthetase ACSL4 in arachidonic acid metabolism.
Prostaglandins Other Lipid Mediat. 144:106363.
2018年業績
Kuwata H, Yuzurihara C, Kinoshita N, Taki Y, Ikegami Y, Washio S, Hirakawa Y, Yoda E, Aiuchi T, Itabe H, Nakatani Y, Hara S.
The group VIA calcium-independent phospholipase A2and NFATc4 pathway mediates IL-1β-induced expression of chemokines CCL2 and CXCL10 in rat fibroblasts
FEBS J. 285:2056-2070.
The group VIA calcium-independent phospholipase A2and NFATc4 pathway mediates IL-1β-induced expression of chemokines CCL2 and CXCL10 in rat fibroblasts
FEBS J. 285:2056-2070.
2017年業績
Nakatani Y, Miyazaki Y, Hara S.
Cytosolic prostaglandin E synthase is involved in c-Fos expression in rat fibroblastic 3Y1 cells.
Biol Pharm Bull. 40: 963-967.
Sasaki Y, Ochiai T, Takamura M, Kondo Y, Yokoyama C, Hara S.
Role of prostacyclin synthase in carcinogenesis.
Prostaglandins Other Lipid Mediat. 133: 49-52.
Hara S.
Prostaglandin terminal synthases as novel therapeutic targets.
Proc Jpn Acad Ser B-Phys Biol Sci. 93: 703-23.
Fujiwara R, Yoda E, Tukey RH.
Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans.
Drug Metab Pharmacokinet. S1347-4367(17): 30137-4.
Yoda E, Paszek M, Konopnicki C, Fujiwara R, Chen S, Tukey RH.
Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress.
Sci Rep. 7: 46489.
Cytosolic prostaglandin E synthase is involved in c-Fos expression in rat fibroblastic 3Y1 cells.
Biol Pharm Bull. 40: 963-967.
Sasaki Y, Ochiai T, Takamura M, Kondo Y, Yokoyama C, Hara S.
Role of prostacyclin synthase in carcinogenesis.
Prostaglandins Other Lipid Mediat. 133: 49-52.
Hara S.
Prostaglandin terminal synthases as novel therapeutic targets.
Proc Jpn Acad Ser B-Phys Biol Sci. 93: 703-23.
Fujiwara R, Yoda E, Tukey RH.
Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans.
Drug Metab Pharmacokinet. S1347-4367(17): 30137-4.
Yoda E, Paszek M, Konopnicki C, Fujiwara R, Chen S, Tukey RH.
Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress.
Sci Rep. 7: 46489.
2016年業績
Arai T, Ohno A, Mori K, Kuwata H, Mizuno M, Imai K, Hara S, Shibanuma M, Kurihara M, Miyata N, Nakagawa H, Fukuhara K.
Inhibition of amyloid fibril formation and cytotoxicity by caffeic acid-conjugated amyloid-β C-terminal peptides.
Bioorg Med Chem Lett. 26: 5468-71.
Arai T, Ohno A, Mori K, Kakizawa T, Kuwata H, Ozawa T, Shibanuma M, Hara S, Ishida S, Kurihara M, Miyata N, Nakagawa H, Fukuhara K.
Design, synthesis, and evaluation of Trolox-conjugated amyloid-β C-terminal peptides for therapeutic intervention in an in vitro model of Alzheimer's disease.
Bioorg Med Chem. 24: 4138-43.
Inhibition of amyloid fibril formation and cytotoxicity by caffeic acid-conjugated amyloid-β C-terminal peptides.
Bioorg Med Chem Lett. 26: 5468-71.
Arai T, Ohno A, Mori K, Kakizawa T, Kuwata H, Ozawa T, Shibanuma M, Hara S, Ishida S, Kurihara M, Miyata N, Nakagawa H, Fukuhara K.
Design, synthesis, and evaluation of Trolox-conjugated amyloid-β C-terminal peptides for therapeutic intervention in an in vitro model of Alzheimer's disease.
Bioorg Med Chem. 24: 4138-43.
2015年業績
Sasaki Y, Kamiyama S, Kamiyama A, Matsumoto K, Akatsu M, Nakatani Y, Kuwata H, Ishikawa Y, Ishii T, Yokoyama C, Hara S.
Genetic-deletion of cyclooxygenase-2 downstream prostacyclin synthase suppresses inflammatory reactions but facilitates carcinogenesis, unlike deletion of microsomal prostaglandin E synthase-1.
Sci Rep. 5: 17376.
Kuwata H, Hara, S.
Inhibition of long-chain acyl-coenzyme A synthetase 4 facilitates production of 5,11-dihydroxyeicosatetraenoic acid via the cyclooxygenase-2 pathway.
Biochem Biophys Res Commun. 465: 525-33.
Sasaki Y, Nakatani Y, Hara S.
Role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived prostaglandin E2 in colon carcinogenesis.
Prostaglandins Other Lipid Mediat. 121: 42-5.
Hara S.
Prostaglandin terminal synthases as novel drug targets.
Bioactive Lipid Mediators: Current Reviews and Protocols (eds. T. Yokomizo & M. Murakami ) Springer 43-57.
桑田浩、原俊太郎
アラキドン酸代謝物産生反応におけるリン脂質リモデリング経路の役割
昭和学士会雑誌 75: 130-7.
Genetic-deletion of cyclooxygenase-2 downstream prostacyclin synthase suppresses inflammatory reactions but facilitates carcinogenesis, unlike deletion of microsomal prostaglandin E synthase-1.
Sci Rep. 5: 17376.
Kuwata H, Hara, S.
Inhibition of long-chain acyl-coenzyme A synthetase 4 facilitates production of 5,11-dihydroxyeicosatetraenoic acid via the cyclooxygenase-2 pathway.
Biochem Biophys Res Commun. 465: 525-33.
Sasaki Y, Nakatani Y, Hara S.
Role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived prostaglandin E2 in colon carcinogenesis.
Prostaglandins Other Lipid Mediat. 121: 42-5.
Hara S.
Prostaglandin terminal synthases as novel drug targets.
Bioactive Lipid Mediators: Current Reviews and Protocols (eds. T. Yokomizo & M. Murakami ) Springer 43-57.
桑田浩、原俊太郎
アラキドン酸代謝物産生反応におけるリン脂質リモデリング経路の役割
昭和学士会雑誌 75: 130-7.
2014年業績
Yoda E, Rai K, Ogawa M, Takakura Y, Kuwata H, Suzuki H, Nakatani Y, Murakami M, Hara S.
Group VIB calcium-independent phospholipase A2 (iPLA2γ) regulates platelet activation, hemostasis and thrombosis in mice.
PLoS One 9: e109409.
Sato H, Taketomi Y, Ushida A, Isogai Y, Kojima T, Hirabayashi T, Miki Y, Yamamoto K, Nishito Y, Kobayashi T, Ikeda K, Taguchi R, Hara S, Ida S, Miyamoto Y, Watanabe M, Baba H, Miyata K, Oike Y, Gelb MH, Murakami M.
The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity.
Cell Metab. 20: 119-32.
Sasabe N, Keyamura Y, Obama T, Inoue N, Masuko K, Igarashi Y, Aiuchi T, Kato R, Yamaguchi T, Kuwata H, Iwamoto S, Miyazaki A, Hara S, Yoshikawa T, Itabe H.
Time course-changes in phosphatidylcholine profile during oxidative modification of low-density lipoprotein.
Lipids Health Dis. 13: 48.
Kuwata H, Yoshimura M, Sasaki Y, Yoda E, Nakatani Y, Kudo I, Hara, S.
Role of long-chain acyl-coenzyme A synthetases in the regulation of arachidonic acid metabolism in interleukin 1β-stimulated rat fibroblasts.
Biochim Biophys Acta ? Mol Cell Biol Lipids 1841: 44-53.
Group VIB calcium-independent phospholipase A2 (iPLA2γ) regulates platelet activation, hemostasis and thrombosis in mice.
PLoS One 9: e109409.
Sato H, Taketomi Y, Ushida A, Isogai Y, Kojima T, Hirabayashi T, Miki Y, Yamamoto K, Nishito Y, Kobayashi T, Ikeda K, Taguchi R, Hara S, Ida S, Miyamoto Y, Watanabe M, Baba H, Miyata K, Oike Y, Gelb MH, Murakami M.
The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity.
Cell Metab. 20: 119-32.
Sasabe N, Keyamura Y, Obama T, Inoue N, Masuko K, Igarashi Y, Aiuchi T, Kato R, Yamaguchi T, Kuwata H, Iwamoto S, Miyazaki A, Hara S, Yoshikawa T, Itabe H.
Time course-changes in phosphatidylcholine profile during oxidative modification of low-density lipoprotein.
Lipids Health Dis. 13: 48.
Kuwata H, Yoshimura M, Sasaki Y, Yoda E, Nakatani Y, Kudo I, Hara, S.
Role of long-chain acyl-coenzyme A synthetases in the regulation of arachidonic acid metabolism in interleukin 1β-stimulated rat fibroblasts.
Biochim Biophys Acta ? Mol Cell Biol Lipids 1841: 44-53.
2013年業績
Ozawa A, Kadowaki E, Haga Y, Sekiguchi H, Hemmi N, Kaneko T, Maki T, Sakabe K, Hara S, Yamamoto M, Arishima K, Sakaue M.
Acetylcholine esterase is a regulator of GFAP expression and a target of dichlorvos in astrocytic differentiation of rat glioma C6 cells.
Brain Res. 1537: 37-45.
Nose F, Yamaguchi T, Kato R, Aiuchi T, Obama T, Hara S, Yamamoto M, Itabe H.
Crucial role of perilipin-3 (TIP47) in formation of lipid droplets and PGE2 production in HL-60-derived neutrophils.
PLoS One 8: e71542.
Miki Y, Yamamoto K, Taketomi Y, Sato H, Shimo K, Kobayashi T, Ishikawa Y, Ishii T, Nakanishi H, Ikeda K, Taguchi R, Kabashima K, Arita M, Arai H, Lambeau G, Bollinger JM, Hara S, Gelb MH, Murakami M.
Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators.
J Exp Med 210: 1217-34.
Taketomi Y, Ueno N, Kojima T, Sato H, Murase R, Yamamoto K, Tanaka S, Sakanaka M, Nakamura M, Nishito Y, Kawana M, Kambe N, Ikeda K, Taguchi R, Nakamizo S, Kabashima K, Gelb MH, Arita M, Yokomizo T, Nakamura M, Watanabe K, Hirai H, Nakamura M, Okayama Y, Ra C, Aritake K, Urade Y, Morimoto K, Sugimoto Y, Shimizu T, Narumiya S, Hara S, Murakami M.
Mast cell maturation is driven via a novel group III phospholipase A2?prostaglandin D2?DP1 receptor paracrine axis.
Nat Immunol. 14: 554-63.
Akitake Y, Nakatani Y, Kamei D, Hosokawa M, Akatsu H, Uematsu S, Akira S, Kudo I, Hara S, Takahashi M.
Microsomal prostaglandin E synthase-1 is induced in Alzheimer's disease and its deletion mitigates Alzheimer's disease-like pathology in a mouse model.
J Neurosci Res. 91: 909-19.
佐々木由香、原俊太郎
創薬の標的としてのプロスタグランジン最終合成酵素群
横溝岳彦 監修 遺伝子医学MOOK24号「最新生理活性脂質研究?実験手法，基礎的研究とその応用?」 メディカルドゥ 146-53.
Acetylcholine esterase is a regulator of GFAP expression and a target of dichlorvos in astrocytic differentiation of rat glioma C6 cells.
Brain Res. 1537: 37-45.
Nose F, Yamaguchi T, Kato R, Aiuchi T, Obama T, Hara S, Yamamoto M, Itabe H.
Crucial role of perilipin-3 (TIP47) in formation of lipid droplets and PGE2 production in HL-60-derived neutrophils.
PLoS One 8: e71542.
Miki Y, Yamamoto K, Taketomi Y, Sato H, Shimo K, Kobayashi T, Ishikawa Y, Ishii T, Nakanishi H, Ikeda K, Taguchi R, Kabashima K, Arita M, Arai H, Lambeau G, Bollinger JM, Hara S, Gelb MH, Murakami M.
Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators.
J Exp Med 210: 1217-34.
Taketomi Y, Ueno N, Kojima T, Sato H, Murase R, Yamamoto K, Tanaka S, Sakanaka M, Nakamura M, Nishito Y, Kawana M, Kambe N, Ikeda K, Taguchi R, Nakamizo S, Kabashima K, Gelb MH, Arita M, Yokomizo T, Nakamura M, Watanabe K, Hirai H, Nakamura M, Okayama Y, Ra C, Aritake K, Urade Y, Morimoto K, Sugimoto Y, Shimizu T, Narumiya S, Hara S, Murakami M.
Mast cell maturation is driven via a novel group III phospholipase A2?prostaglandin D2?DP1 receptor paracrine axis.
Nat Immunol. 14: 554-63.
Akitake Y, Nakatani Y, Kamei D, Hosokawa M, Akatsu H, Uematsu S, Akira S, Kudo I, Hara S, Takahashi M.
Microsomal prostaglandin E synthase-1 is induced in Alzheimer's disease and its deletion mitigates Alzheimer's disease-like pathology in a mouse model.
J Neurosci Res. 91: 909-19.
佐々木由香、原俊太郎
創薬の標的としてのプロスタグランジン最終合成酵素群
横溝岳彦 監修 遺伝子医学MOOK24号「最新生理活性脂質研究?実験手法，基礎的研究とその応用?」 メディカルドゥ 146-53.
2012年業績
Mita M, Satoh M, Shimada A, Azuma S, Himeno S, Hara S.
Metallothionein deficiency exacerbates chronic inflammation associated with carcinogenesis in stomach of mice infected with Helicobacter pylori.
J Toxicol Sci. 37: 1261-65.
Kuroki Y, Sasaki Y, Kamei D, Akitake Y, Takahashi M, Uematsu S, Akira S, Nakatani Y, Kudo I, Hara S.
Deletion of microsomal prostaglandin E synthase-1 protects neuronal cells from cytotoxic effects of β-amyloid peptide fragment 31-35.
Biochem Biophys Res Commun. 424: 409-13.
Yoshioka W, Aida-Yasuoka K, Fujisawa N, Kawaguchi T, Ohsako S, Hara S, Uematsu S, Akira S, Tohyama C.
Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice.
Toxicol Sci. 127: 547-54.
Sasaki Y, Kamei D, Ishikawa Y, Ishii T, Uematsu S, Akira S, Murakami M, Hara S.
Microsomal prostaglandin E synthase-1 is involved in multiple steps of colon carcinogenesis.
Oncogene. 31: 2943-52.
中谷良人
細胞質型プロスタグランジンE2合成酵素
昭和大学薬学雑誌 3: 27-34.
Metallothionein deficiency exacerbates chronic inflammation associated with carcinogenesis in stomach of mice infected with Helicobacter pylori.
J Toxicol Sci. 37: 1261-65.
Kuroki Y, Sasaki Y, Kamei D, Akitake Y, Takahashi M, Uematsu S, Akira S, Nakatani Y, Kudo I, Hara S.
Deletion of microsomal prostaglandin E synthase-1 protects neuronal cells from cytotoxic effects of β-amyloid peptide fragment 31-35.
Biochem Biophys Res Commun. 424: 409-13.
Yoshioka W, Aida-Yasuoka K, Fujisawa N, Kawaguchi T, Ohsako S, Hara S, Uematsu S, Akira S, Tohyama C.
Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice.
Toxicol Sci. 127: 547-54.
Sasaki Y, Kamei D, Ishikawa Y, Ishii T, Uematsu S, Akira S, Murakami M, Hara S.
Microsomal prostaglandin E synthase-1 is involved in multiple steps of colon carcinogenesis.
Oncogene. 31: 2943-52.
中谷良人
細胞質型プロスタグランジンE2合成酵素
昭和大学薬学雑誌 3: 27-34.
2011年業績
Nakatani Y, Hokonohara Y, Tajima Y, Kudo I, Hara S.
Involvement of the constitutive prostaglandin E synthase cPGES/p23 in expression of an initial prostaglandin E2 inactivating enzyme, 15-PGDH.
Prostaglandins Other Lipid Mediat. 94: 112-117.
Sato H, Isogai Y, Masuda S, Taketomi Y, Miki Y, Kamei D, Hara S, Kobayashi T, Ishikawa Y, Ishii T, Ikeda K, Taguchi R, Ishimoto Y, Suzuki N, Yokota Y, Hanasaki K, Suzuki-Yamamoto T, Yamamoto K, Murakami M.
Physiological roles of group X-secreted phospholipase A2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function.
J Biol Chem. 286(13): 11632-48.
Yamamoto K, Taketomi Y, Isogai Y, Miki Y, Sato H, Masuda S, Nishito Y, Morioka K, Ishimoto Y, Suzuki N, Yokota Y, Hanasaki K, Ishikawa Y, Ishii T, Kobayashi T, Fukami K, Ikeda K, Nakanishi H, Taguchi R, Murakami M.
Hair follicular expression and function of group x secreted phospholipase A2 in mouse skin.
J Biol Chem. 286(13): 11616-31.
Involvement of the constitutive prostaglandin E synthase cPGES/p23 in expression of an initial prostaglandin E2 inactivating enzyme, 15-PGDH.
Prostaglandins Other Lipid Mediat. 94: 112-117.
Sato H, Isogai Y, Masuda S, Taketomi Y, Miki Y, Kamei D, Hara S, Kobayashi T, Ishikawa Y, Ishii T, Ikeda K, Taguchi R, Ishimoto Y, Suzuki N, Yokota Y, Hanasaki K, Suzuki-Yamamoto T, Yamamoto K, Murakami M.
Physiological roles of group X-secreted phospholipase A2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function.
J Biol Chem. 286(13): 11632-48.
Yamamoto K, Taketomi Y, Isogai Y, Miki Y, Sato H, Masuda S, Nishito Y, Morioka K, Ishimoto Y, Suzuki N, Yokota Y, Hanasaki K, Ishikawa Y, Ishii T, Kobayashi T, Fukami K, Ikeda K, Nakanishi H, Taguchi R, Murakami M.
Hair follicular expression and function of group x secreted phospholipase A2 in mouse skin.
J Biol Chem. 286(13): 11616-31.
2010年業績
Yoda E, Hachisu K, Taketomi Y, Yoshida K, Nakamura M, Ikeda K, Taguchi R, Nakatani Y, Kuwata H, Murakami M, Kudo I, Hara S.
Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of Group VIB Ca2+-independent phospholipase A2gamma-deficient mice.
J Lipid Res. 51(10): 3003-15.
Hara S, Kamei D, Sasaki Y, Tanemoto A, Nakatani Y, Murakami M.
Prostaglandin E synthases: understanding their pathophysiological roles through mouse genetic models.
Biochimie 92(6): 651-9.
Escoffier J, Jemel I, Tanemoto A, Taketomi Y, Payre C, Coatrieux C, Sato H, Yamamoto K, Masuda S, Pernet-Gallay K, Pierre V, Hara S, Murakami M, De Waard M, Lambeau G, Arnoult C.
Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice.
J Clin Invest. 120(5): 1415-28.
Sato H, Taketomi Y, Isogai Y, Miki Y, Yamamoto K, Masuda S, Hosono T, Arata S, Ishikawa Y, Ishii T, Kobayashi T, Nakanishi H, Ikeda K, Taguchi R, Hara S, Kudo I, Murakami M.
Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice.
J Clin Invest. 120(5): 1400-14.
Suzuki Y, Kondo Y, Hara S, Kimata R, Nishimura T.
Effect of the hsp90 inhibitor geldanamycin on androgen response of prostate cancer under hypoxic conditions.
Int J Urol. 17(3): 281-5.
Kamei D, Murakami M, Sasaki Y, Nakatani Y, Majima M, Ishikawa Y, Ishii T, Uematsu S, Akira S, Hara S, Kudo I.
Microsomal prostaglandin E synthase-1 in both cancer cells and host contributes to tumour growth, invasion and metastasis.
Biochem J. 425(2): 361-71.
Sugita M, Kuwata H, Kudo I, Hara S.
Differential contribution of protein kinase C isoforms in the regulation of group IIA secreted phospholipase A2 expression in cytokine-stimulated rat fibroblasts.
Biochim Biophys Acta. 1801(1): 70-6.
Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of Group VIB Ca2+-independent phospholipase A2gamma-deficient mice.
J Lipid Res. 51(10): 3003-15.
Hara S, Kamei D, Sasaki Y, Tanemoto A, Nakatani Y, Murakami M.
Prostaglandin E synthases: understanding their pathophysiological roles through mouse genetic models.
Biochimie 92(6): 651-9.
Escoffier J, Jemel I, Tanemoto A, Taketomi Y, Payre C, Coatrieux C, Sato H, Yamamoto K, Masuda S, Pernet-Gallay K, Pierre V, Hara S, Murakami M, De Waard M, Lambeau G, Arnoult C.
Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice.
J Clin Invest. 120(5): 1415-28.
Sato H, Taketomi Y, Isogai Y, Miki Y, Yamamoto K, Masuda S, Hosono T, Arata S, Ishikawa Y, Ishii T, Kobayashi T, Nakanishi H, Ikeda K, Taguchi R, Hara S, Kudo I, Murakami M.
Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice.
J Clin Invest. 120(5): 1400-14.
Suzuki Y, Kondo Y, Hara S, Kimata R, Nishimura T.
Effect of the hsp90 inhibitor geldanamycin on androgen response of prostate cancer under hypoxic conditions.
Int J Urol. 17(3): 281-5.
Kamei D, Murakami M, Sasaki Y, Nakatani Y, Majima M, Ishikawa Y, Ishii T, Uematsu S, Akira S, Hara S, Kudo I.
Microsomal prostaglandin E synthase-1 in both cancer cells and host contributes to tumour growth, invasion and metastasis.
Biochem J. 425(2): 361-71.
Sugita M, Kuwata H, Kudo I, Hara S.
Differential contribution of protein kinase C isoforms in the regulation of group IIA secreted phospholipase A2 expression in cytokine-stimulated rat fibroblasts.
Biochim Biophys Acta. 1801(1): 70-6.
2009年業績
Hatanaka M, Shimba S, Sakaue M, Kondo Y, Kagechika H, Kokame K, Miyata T, Hara, S.
Hypoxia-inducible factor-3alpha functions as an accelerator of 3T3-L1 adipose differentiation.
Biol Pharm Bull 72(7):1166-72.
Sakaue M, Mori N, Makita M, Fujishima K, Hara S, Arishima K, Yamamoto M.
Acceleration of methylmercury-induced cell death of rat cerebellar neurons by brain-derived neurotrophic factor in vitro.
Brain Res. 1273:155-62.
Ishioka J, Hara S, Isaacs JT, Tomura A, Nishikawa K, Kageyama Y.
Suppression of mutant androgen receptors by flutamide.
Int J Urol. 16(5):516-21.
Fujino T, Murakami K, Ozawa I, Minegishi Y, Kashimura R, Akita T, Saitou S, Atsumi T, Sato T, Ando K, Hara S, Kikugawa K, Hayakawa M.
Hypoxia downregulates farnesoid X receptor via a hypoxia-inducible factor-independent but p38 mitogen-activated protein kinase-dependent pathway.
FEBS J. 276(5):1319-32.
Hypoxia-inducible factor-3alpha functions as an accelerator of 3T3-L1 adipose differentiation.
Biol Pharm Bull 72(7):1166-72.
Sakaue M, Mori N, Makita M, Fujishima K, Hara S, Arishima K, Yamamoto M.
Acceleration of methylmercury-induced cell death of rat cerebellar neurons by brain-derived neurotrophic factor in vitro.
Brain Res. 1273:155-62.
Ishioka J, Hara S, Isaacs JT, Tomura A, Nishikawa K, Kageyama Y.
Suppression of mutant androgen receptors by flutamide.
Int J Urol. 16(5):516-21.
Fujino T, Murakami K, Ozawa I, Minegishi Y, Kashimura R, Akita T, Saitou S, Atsumi T, Sato T, Ando K, Hara S, Kikugawa K, Hayakawa M.
Hypoxia downregulates farnesoid X receptor via a hypoxia-inducible factor-independent but p38 mitogen-activated protein kinase-dependent pathway.
FEBS J. 276(5):1319-32.
2008年業績
Sato H, Kato R, Isogai Y, Saka G, Ohtsuki M, Taketomi Y, Yamamoto K, Tsutsumi K, Yamada J, Masuda S, Ishikawa Y, Ishii T, Kobayashi T, Ikeda K, Taguchi R, Hatakeyama S, Hara S, Kudo I, Itabe H, Murakami M.
Analyses of group III secreted phospholipase A2 transgenic mice reveal potential participation of this enzyme in plasma lipoprotein modification, macrophage foam cell formation, and atherosclerosis.
J Biol Chem. 283(48):33483-97.
Sakaue M, Mori N, Okazaki M, Ishii M, Inagaki Y, Iino Y, Miyahara K, Yamamoto M, Kumagai T, Hara S, Yamamoto M, Arishima K.
Involvement of independent mechanism upon poly(ADP-ribose) polymerase (PARP) activation in methylmercury cytotoxicity in rat cerebellar granule cell culture.
J Neurosci Res. 86(15):3427-34.
Ueno N, Taketomi Y, Koga K, Atsumi Y, Kikuchi-Yanoshita R, Kudo I, Murakami M.
A negative regulator of delayed prostaglandin D2 production in mouse mast cells.
Biochim Biophys Acta. 1781(8):415-21.
Takano H, Nakazawa S, Okuno Y, Shirata N, Tsuchiya S, Kainoh T, Takamatsu S, Furuta K, Taketomi Y, Naito Y, Takematsu H, Kozutsumi Y, Tsujimoto G, Murakami M, Kudo I, Ichikawa A, Nakayama K, Sugimoto Y, Tanaka S.
Establishment of the culture model system that reflects the process of terminal differentiation of connective tissue-type mast cells.
FEBS Lett. 582(10):1444-50.
Mita M, Satoh M, Shimada A, Okajima M, Azuma S, Suzuki JS, Sakabe K, Hara S, Himeno S.
Metallothionein is a crucial protective factor against Helicobacter pylori-induced gastric erosive lesions in a mouse model.
Am J Physiol Gastrointest Liver Physiol. 294(4):G877-84.
Yamakawa K, Kamekura S, Kawamura N, Saegusa M, Kamei D, Murakami M, Kudo I, Uematsu S, Akira S, Chung UI, Nakamura K, Kawaguchi H.
Association of microsomal prostaglandin E synthase 1 deficiency with impaired fracture healing, but not with bone loss or osteoarthritis, in mouse models of skeletal disorders.
Arthritis Rheum. 58(1):172-83.
Masuda S, Yamamoto K, Hirabayashi T, Ishikawa Y, Ishii T, Kudo I, Murakami M.
Human group III secreted phospholipase A2 promotes neuronal outgrowth and survival.
Biochem J. 409(2):429-38.
Analyses of group III secreted phospholipase A2 transgenic mice reveal potential participation of this enzyme in plasma lipoprotein modification, macrophage foam cell formation, and atherosclerosis.
J Biol Chem. 283(48):33483-97.
Sakaue M, Mori N, Okazaki M, Ishii M, Inagaki Y, Iino Y, Miyahara K, Yamamoto M, Kumagai T, Hara S, Yamamoto M, Arishima K.
Involvement of independent mechanism upon poly(ADP-ribose) polymerase (PARP) activation in methylmercury cytotoxicity in rat cerebellar granule cell culture.
J Neurosci Res. 86(15):3427-34.
Ueno N, Taketomi Y, Koga K, Atsumi Y, Kikuchi-Yanoshita R, Kudo I, Murakami M.
A negative regulator of delayed prostaglandin D2 production in mouse mast cells.
Biochim Biophys Acta. 1781(8):415-21.
Takano H, Nakazawa S, Okuno Y, Shirata N, Tsuchiya S, Kainoh T, Takamatsu S, Furuta K, Taketomi Y, Naito Y, Takematsu H, Kozutsumi Y, Tsujimoto G, Murakami M, Kudo I, Ichikawa A, Nakayama K, Sugimoto Y, Tanaka S.
Establishment of the culture model system that reflects the process of terminal differentiation of connective tissue-type mast cells.
FEBS Lett. 582(10):1444-50.
Mita M, Satoh M, Shimada A, Okajima M, Azuma S, Suzuki JS, Sakabe K, Hara S, Himeno S.
Metallothionein is a crucial protective factor against Helicobacter pylori-induced gastric erosive lesions in a mouse model.
Am J Physiol Gastrointest Liver Physiol. 294(4):G877-84.
Yamakawa K, Kamekura S, Kawamura N, Saegusa M, Kamei D, Murakami M, Kudo I, Uematsu S, Akira S, Chung UI, Nakamura K, Kawaguchi H.
Association of microsomal prostaglandin E synthase 1 deficiency with impaired fracture healing, but not with bone loss or osteoarthritis, in mouse models of skeletal disorders.
Arthritis Rheum. 58(1):172-83.
Masuda S, Yamamoto K, Hirabayashi T, Ishikawa Y, Ishii T, Kudo I, Murakami M.
Human group III secreted phospholipase A2 promotes neuronal outgrowth and survival.
Biochem J. 409(2):429-38.
2007年業績
Mitsuishi M, Masuda S, Kudo I, Murakami M.
Human group III phospholipase A2 suppresses adenovirus infection into host cells. Evidence that group III, V and X phospholipase A2s act on distinct cellular phospholipid molecular species.
Biochim Biophys Acta. 1771(11):1389-96.
Moon TC, Quan Z, Kim J, Kim HP, Kudo I, Murakami M, Park H, Chang HW.
Inhibitory effect of synthetic C-C biflavones on various phospholipase A2s activity.
Bioorg Med Chem. 15(22):7138-43.
Nakatani Y, Hokonohara Y, Kakuta S, Sudo K, Iwakura Y, Kudo I.
Knockout mice lacking cPGES/p23, a constitutively expressed PGE2 synthetic enzyme, are peri-natally lethal.
Biochem Biophys Res Commun. 362(2):387-92.
Nakatani Y
Regulation of cytosolic prostaglandin E synthase.
J. Health Sci. 53(3):251-256
Taketomi Y, Sunaga K, Tanaka S, Nakamura M, Arata S, Okuda T, Moon TC, Chang HW, Sugimoto Y, Kokame K, Miyata T, Murakami M, Kudo I.
Impaired mast cell maturation and degranulation and attenuated allergic responses in Ndrg1-deficient mice.
J Immunol. 178(11):7042-53.
Kuwata H, Fujimoto C, Yoda E, Shimbara S, Nakatani Y, Hara S, Murakami M, Kudo I.
A novel role of group VIB calcium-independent phospholipase A2 (iPLA2gamma) in the inducible expression of group IIA secretory PLA2 in rat fibroblastic cells.
J Biol Chem. 282(28):20124-32.
Horii K, Suzuki Y, Kondo Y, Akimoto M, Nishimura T, Yamabe Y, Sakaue M, Sano T, Kitagawa T, Himeno S, Imura N, Hara S.
Androgen-dependent gene expression of prostate-specific antigen is enhanced synergistically by hypoxia in human prostate cancer cells.
Mol Cancer Res. 5(4):383-91.
Urushibara M, Ishioka J, Hyochi N, Kihara K, Hara S, Singh P, Isaacs JT, Kageyama Y.
Effects of steroidal and non-steroidal antiandrogens on wild-type and mutant androgen receptors.
Prostate. 67(8):799-807.
Nakatani Y, Chin Y, Hara S, Kudo I.
Immediate prostaglandin E2 synthesis in rat 3Y1 fibroblasts following vasopressin V1a receptor stimulation.
Biochem Biophys Res Commun. 354(3):676-80.
Ohtsuki M, Taketomi Y, Arata S, Masuda S, Ishikawa Y, Ishii T, Takanezawa Y, Aoki J, Arai H, Yamamoto K, Kudo I, Murakami M.
Transgenic expression of group V, but not group X, secreted phospholipase A2 in mice leads to neonatal lethality because of lung dysfunction.
J Biol Chem. 281(47):36420-33.
Human group III phospholipase A2 suppresses adenovirus infection into host cells. Evidence that group III, V and X phospholipase A2s act on distinct cellular phospholipid molecular species.
Biochim Biophys Acta. 1771(11):1389-96.
Moon TC, Quan Z, Kim J, Kim HP, Kudo I, Murakami M, Park H, Chang HW.
Inhibitory effect of synthetic C-C biflavones on various phospholipase A2s activity.
Bioorg Med Chem. 15(22):7138-43.
Nakatani Y, Hokonohara Y, Kakuta S, Sudo K, Iwakura Y, Kudo I.
Knockout mice lacking cPGES/p23, a constitutively expressed PGE2 synthetic enzyme, are peri-natally lethal.
Biochem Biophys Res Commun. 362(2):387-92.
Nakatani Y
Regulation of cytosolic prostaglandin E synthase.
J. Health Sci. 53(3):251-256
Taketomi Y, Sunaga K, Tanaka S, Nakamura M, Arata S, Okuda T, Moon TC, Chang HW, Sugimoto Y, Kokame K, Miyata T, Murakami M, Kudo I.
Impaired mast cell maturation and degranulation and attenuated allergic responses in Ndrg1-deficient mice.
J Immunol. 178(11):7042-53.
Kuwata H, Fujimoto C, Yoda E, Shimbara S, Nakatani Y, Hara S, Murakami M, Kudo I.
A novel role of group VIB calcium-independent phospholipase A2 (iPLA2gamma) in the inducible expression of group IIA secretory PLA2 in rat fibroblastic cells.
J Biol Chem. 282(28):20124-32.
Horii K, Suzuki Y, Kondo Y, Akimoto M, Nishimura T, Yamabe Y, Sakaue M, Sano T, Kitagawa T, Himeno S, Imura N, Hara S.
Androgen-dependent gene expression of prostate-specific antigen is enhanced synergistically by hypoxia in human prostate cancer cells.
Mol Cancer Res. 5(4):383-91.
Urushibara M, Ishioka J, Hyochi N, Kihara K, Hara S, Singh P, Isaacs JT, Kageyama Y.
Effects of steroidal and non-steroidal antiandrogens on wild-type and mutant androgen receptors.
Prostate. 67(8):799-807.
Nakatani Y, Chin Y, Hara S, Kudo I.
Immediate prostaglandin E2 synthesis in rat 3Y1 fibroblasts following vasopressin V1a receptor stimulation.
Biochem Biophys Res Commun. 354(3):676-80.
Ohtsuki M, Taketomi Y, Arata S, Masuda S, Ishikawa Y, Ishii T, Takanezawa Y, Aoki J, Arai H, Yamamoto K, Kudo I, Murakami M.
Transgenic expression of group V, but not group X, secreted phospholipase A2 in mice leads to neonatal lethality because of lung dysfunction.
J Biol Chem. 281(47):36420-33.
2006年業績
Wijewickrama GT, Albanese A, Kim YJ, Oh YS, Murray PS, Takayanagi R, Tobe T, Masuda S, Murakami M, Kudo I, Ucker DS, Murray D, Cho W.
Unique membrane interaction mode of group IIF phospholipase A2.
J Biol Chem. 2006 Oct 27;281(43):32741-54.
Murakami M, Kudo I.
Prostaglandin E synthase: a novel drug target for inflammation and cancer.
Curr Pharm Des. 12(8):943-54. Review.
Nishimoto M, Sakaue M, Hara S.
Short-interfering RNA-mediated silencing of thioredoxin reductase 1 alters the sensitivity of HeLa cells toward cadmium.
Biol Pharm Bull. 29(3):543-6.
Mitsuishi M, Masuda S, Kudo I, Murakami M.
Group V and X secretory phospholipase A2 prevents adenoviral infection in mammalian cells.
Biochem J. 393(Pt 1):97-106.
Unique membrane interaction mode of group IIF phospholipase A2.
J Biol Chem. 2006 Oct 27;281(43):32741-54.
Murakami M, Kudo I.
Prostaglandin E synthase: a novel drug target for inflammation and cancer.
Curr Pharm Des. 12(8):943-54. Review.
Nishimoto M, Sakaue M, Hara S.
Short-interfering RNA-mediated silencing of thioredoxin reductase 1 alters the sensitivity of HeLa cells toward cadmium.
Biol Pharm Bull. 29(3):543-6.
Mitsuishi M, Masuda S, Kudo I, Murakami M.
Group V and X secretory phospholipase A2 prevents adenoviral infection in mammalian cells.
Biochem J. 393(Pt 1):97-106.