職　　歴
1953年 名古屋大学医学部卒業
1959年 大阪大学・蛋白質研究所　助教授
1961年 徳島大学・医学部　教授
1980年〜1982年迄 徳島大学・医学部　医学部長
1987年〜1992年 徳島大学・酵素科学研究センター　センター長
1992年〜 徳島文理大学 教授　兼　健康科学研究所 所長
1996年〜2001年 文部省・ハイテク・リサーチセンター長
2000年〜2006年3月迄 徳島文理大学　兼　徳島文理大学短期大学部　学長
2000年〜 文部科学省・社会連携研究（旧産学連携）　研究組織長
健康科学研究所・生活習慣病部門長
学　　会
日本生化学会　名誉会員
日本ビタミン学会　名誉会員
米国生化学会　名誉会員
米国癌学会　名誉会員
国際ビタミン学会　事務局長
IPS(International Proteolysis Society)　終生名誉会員第1号
スペイン国立細胞学研究所(バレンシア)　名誉所員
ステフィン国立研究所(スロベニア)　名誉所員
Molecular Genetics and Metabolism (Academic Press)　編集者
Bio Factors (IOS Press) 　編集者
Biochemical J.（英生化学誌）　編集者
賞　　罰
昭和62年 剣道教士7段
平成2年 紫綬褒章−−[酵素学の発展に貢献]
平成9年 勲ニ等瑞宝章
研　究　概　要
[1] 　細胞内局在を異にするIsoenzyme（Isozyme,同位酵素）をトランスアミナーゼGOTとGPTにつき発見し、１つはミトコンドリア、他は細胞質に局在して、夫々異なる代謝分担をしている事を明らかにした。以後多くのIsozymeが色々の酵素で発見され、癌の分化度のマーカーとして、また診断法（肝機能や心機能）に世界的に凡用されている。
[2] 　Cathepsin（細胞内システインプロテアーゼ）のＢとＬの発見、それらの細胞内阻害タンパクCystatinαとβを世界で初めて記載した。それ以後、多くのCathepsinとCystatinが国際的に発見され、現在では１０種以上が明らかになった。またCathepsin類の人工阻害剤E-64、CA-074等製薬企業との共同で開発し、現在世界中が使用している。
[3] 　ヒスタミンアレルギー発現に関与するChymaseとTryptaseを、マストセル顆粒中から発見し、構造決定をした。また此等のアレルギー発現との関連を明らかにした。
＊[1][2][3]の研究により、酵素学の発展に貢献した功績により平成２年紫綬褒章を授与された。
[4] 　カテプシンＢ、Ｌ、Ｓ、Ｋに対する夫々の特異的阻害剤をコンピューターグラフィックスによる立体構造から開発して、夫々の生理的役割を追求、またこれらの病的発現による病態を明らかにした。
[5] 　骨崩壊の主因であるコラーゲン分解機構を追及し、此れの主役を演ずるCathepsin　KとLの特異的阻害剤を開発して、骨分解や癌の骨転移抑制に道を開拓しつつある。
[6] 　多くの基本的生命現象・病態形成および老化の根本現象であり、現在、最も重要視されている細胞のプログラミング死（アポトーシス）を誘導する新しい酵素Lysoapoptaseをリソゾーム中に発見して、構造決定をしている。此の抑制法は重症肝障害の抑制及び癌細胞をアポトーシスに導くことによる新癌治療戦略の開発を目指している。
[7] 　自己免疫病シーグレン病と１型糖尿病の抗原提示がカテプシンSの阻害剤で抑制できることを明らかにした。
※[5][6][7]は現在進行中の研究である。
主　要　論　文
1) Katunuma, N., Ohashi, A., Sano, E., Ishimaru, N., Hayashi, Y., Murata, E.:
Catechin derivatives: specific inhibitor for caspases-3, 7 and 2, and the prevention of apoptosis at the cell and animal levels,
FEBS Lett, 580, 741-746 (2006)
2) Katunuma, N., Le, QT., Murata, E., Matsui, A., Majima, E., Ishimaru, N., Hayashi, Y., Ohashi, A.:
A novel apoptosis cascade mediated by lysosomal lactoferrin and its participation in hepatocyte apopotosis induced by d-galactosamine,
FEBS-Lett, 580, 3699-3705 (2006)
3) Le, QT., Ohashi, A., Hirose, S., Katunuma, N.:
Reverse zymography using fluorogenic substrated for protease inhibitor detection,
Electrophoresis, 26, 1038-1045 (2005)
4) N. Katunuma, E. Murata, H. Kakegawa, A. Matsui, H. Tsuzuki, H. Tsuge, D. Turk, V. Turk, M. Fukushima, Y. Tada, T. Asao:
Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo;
FEBS-Lett, 458, 6-10 (1999)
5) T. Towatari, T. Nikawa, M. Murata, C. Yokoo, M. Tamai, K. Hanada and N. Katunuma:
Novel Epoxysuccinyl Peptides; A Selective Inhibitor of Cathepsin B in Vivo,
FEBS-Lett. 280(2), 311-315 (1991)
6) E. Kominami, N. Wakamatsu and N. Katunuma:
Purification and Characterization of Thiol Proteinase Inhibitors from Rat Serum and Liver,
J. Biol. Chem. 257(24), 14648-14652 (1982)
最近5年間の英文論文リスト
1) Valerie Laurent-Matha, Danielle Derocq, Christine Prebois, Nobuhiko Katunuma, and Emmanuelle Liaudet-Coopman:
Processing of Humana Cathepsin D Is Independent of Its Catalytic Function and Auto-Activation: Involvement of Cathepsins L and B.
JB. 139, 363-371 (2006)
2) Katunuma N, Ohashi A, Sano E, Ishimaru N, Hayashi Y, Murata E.:
Catechin derivatives: specific inhibitor for caspases-3, 7 and 2, and the prevention of apoptosis at the cell and animal levels.
FEBS Lett. 580, 741-746 (2006)
3) Katunuma N, Le QT, Murata E, Matsui A, Majima E, Ishimaru N, Hayashi Y, Ohashi A.:
A novel apoptosis cascade mediated by lysosomal lactoferrin and its participation in hepatocyte apoptosis induced by d-galactosamine.
FEBS Lett. 580, 3699-3705 (2006)
4) Ago H, Oda M, Takahashi M, Tsuge H, Ochi S, Katunuma N, Miyano M, Sakurai J.:
Structural basis of the sphingomyelin phosphodiesterase activity in neutral sphingomyelinase from Bacillus cereus.
J Biol Chem. 281, 16157-16167 (2006)
5) Yoko Hashimoto, Chihiro Kondo, Takashi Kojima, Hiroshi Nagata, Akihiko Moriyama, Taro Hayakawa, and Nobuhiko Katunuma.:
Significance of 32-kDa cathepsin L secreted from cancer cells.
Cancer Biotherapy and Radiopharmaceutical. (2006) in press
6) Etuko Sano, Risa Miyauchi, Natsuko Takakura, Koji Yamauchi, Etuko Murata, and Nobuhiko Katunuma.:
Cysteine protease inhibitors in various milk preparations and its importance as a food.
Food Research International. 38, 427-433 (2005)
7) Le QT, Ohashi A, Hirose S, Katunuma N.:
Reverse zymography using fluorogenic substrated for protease inhibitor detection.
Electrophoresis. 26, 1038-1045 (2005)
8) Bhuiya MW, Sakuraba H, Ohshima T, Imagawa T, Katunuma N, Tsuge H.:
The First Crystal Structure of Hyperthermostable NAD-dependent Glutamate Dehydrogenase from Pyrobaculum islandicum;
J Mol Biol. 345, 325-337 (2005)
9) Sakuraba H, Tsuge H, Yoneda K, Katunuma N, Ohshima T.:
Crystal structure of the NAD biosynthetic enzyme quinolinate synthase.
J. Biol. Chem. 280, 26645-26648 (2005)
10) Kawakami R, Sakuraba H, Tsuge H, Goda S, Katunuma N, Ohshima T.:
A second novel dye-linked L-proline dehydrogenase complex is present in the hyperthermophilic archaeon Pyrococcus horikoshii OT-3.
FEBS-Lett. 272, 4044-4054 (2005)
11) Tsuge H, Kawakami R, Sakuraba H, Ago H, Miyano M, Aki K, Katunuma N, Ohshima T.:
Crystal structure of novel FAD, FMN and ATP-containing L-proline dehydrogenase complex from pyrococcus horikoshii.
J. Biol. Chem. 280, 31045-31049 (2005)
12) Inubushi T, Takasawa T, Tuboi Y, Watanage N, Aki K, Katunuma N.:
Changes of glucose metabolism and skin-collagen neogenesis in vitamin B6 deficiency.
Biofactors. 23, 59-67 (2005)
13) Katunuma N, Le QT, Miyauchi R, Hirose S.:
Double-layar fluorescent zymography for processing protease detection.
Anal Biochem. 347, 208-212 (2005)
14) Kitamura H, Kamon H, Sawa S, Park SJ, Katunuma N, Ishihara K, Murakami M, Hirano T.:
IL-6-STAT3 controls intracellular MHC class II alphabeta dimer level through cathepsin S activity in dendritic cells.
Immunity. 23, 491-502 (2005)
15) Le QT, Katunuma N.: Detection of protease inhibitors by a reverse zymography method, performed in a tris(hydroxymethyl)aminomethane-Tricine buffer system. Anal. Biochem. 324, 237-240 (2004)
16) Kakegawa H, Matano Y, Inubushi T, Katunuma N.: Significant accumulations of cathepsin B and prolylendopeptidase in inflammatory focus of delayed-type hypersensitivity induced by Mycobacterium tuberculosis in mice. Biochem Biophys Res Commun. 316(1), 78-84 (2004)
17) Imagawa T, Nakayama H, Katunuma N, Sakuraba H, Ohshima T, Itoh T, Sako Y, Nomura N, Tsuge H.:
Crystallization and preliminary X-ray diffraction analysis of homing endonuclease I-Tsp061I.
Acta Crystallogr D Biol Crystallogr. 60, 2006-2008 (2004)
18) Onishi K, Li Y, Ishii K, Hisaeda H, Tang L, Duan X, Dainichi T, Maekawa Y, Katunuma N, Himeno K.:
Cathepsin L is crucial for a Th1-type immune response during Leishmania major infection.
Microbes Infect. 6, 468-474 (2004)
19) Bhuiya MW, Sakuraba H, Yoneda K, Ohshima T, Imagawa T, Katunuma N, Tsuge H.:
Crystallization and preliminary X-ray diffraction analysis of the hyperthermostable NAD-dependent glutamate dehydrogenase from Pyrobaculum islandicum.
Acta Crystallogr D Biol Crystallogr. 60, 715-717 (2004)
20) Toshiyuki Nomura, and Nobuhiko Katunuma.:
Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells.
The Journal of Medical Investigation. 52, 1-9 (2004) REVIEW
21) Tsugawa Junko, Inubushi Tomoko, Murata Etsuko, Kakegawa Hisao, and Katunuma Nobuhiko.:
Novel biological function of vitamin B6 derivatives as cysteine protease inhibitor and their effects to antigen presentation and bone resorption.
The 3rd Japan-China International Conference on Vitamins, 7-18 (2004)
22) Ishimaru N, Arakaki R, Katunuma N, Hayashi Y.:
Critical role of cathepsin-inhibitors for autoantigen processing and autoimmunity.
Advan. Enzyme Regul. 44, 309-320 (2004)
23) Katunuma N, Murata E, Le QT, Hayashi Y, Ohashi A.:
New apoptosis cascade mediated by lysosomal enzyme and its protection by epigallo-catechin gallate.
Advan. Enzyme Regul. 44, 1-10 (2004)
24) Tomoko Kadowaki, Shizuo Kitano, Atsuyo Baba, Ryosuke Takii, Munetaka Hashimoto, Nobuhiko Katunuma, and Kenji Yamamoto: Isolation and Characterization of a Novel and Potent inhibitor of Arggingipain from Streptomyces sp. Strain FA-70 Biological Chemistry 384, 911-920 (2003)
25) Gao HZ, Kobayashi K, Tabata A, Tsuge H, Iijima M, Yasuda T, Kalkanoglu HS, Dursun A, Tokatli A, Coskun T, Trefz FK, Skladal D, Mandel H, Seidel J, Kodama S, Shirane S, Ichida T, Makino S, Yoshino M, Kang JH, Mizuguchi M, Barshop BA, Fuchinoue S, Seneca S, Zeesman S, Knerr I, Rodes M, Wasant P, Yoshida I, De Meirleir L, Abdul Jalil M, Begum L, Horiuchi M, Katunuma N, Nakagawa S, Saheki T.: Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients. Hum Mutat. 22(1), 24-34 (2003)
26) Hideaki Tsuge, Masahiro Nagahama, Hiroyuki Nishimura, Junzo Hisatsune, Yoshihiko Sakaguchi, Yasuhiro Itogawa, Nobuhiko Katunuma and Jun Sakurai: Crystal Structure and Site-directed Mutagenesis of Enzymatic Components from Clostridium perfringens Iota-toxin. J. Mol. Biol. 325, 471-483 (2003)
27) Haruhiko Sakuraba, Hideaki Tsuge, Ikuko Shimoya, Ryushi Kawakami, Shuichiro Goda, Yutaka Kawarabayashi, Nobuhiko Katunuma, Hideo Ago, Masashi Miyano, and Toshihisa Ohshima:
The First Crystal Structure of Archaeal Aldolase. Unique tetrameric structure of 2-deoxy-d-ribose-5-phosphate aldolase from the hyperthermophilic archaea Aeropyrum pernix. The Journal of Biological Chemistry. 278(12), 10799-10806 (2003)
28) A. Ohashi, E. Murata, K. Yamamoto, E. Majima, E. Sano, Q. T. Le and N. Katunuma: New functions of lactoferrin and b-casein in mammalian milk as cysteine protease inhibitors. BBRC 306, 98-103 (2003)
29) N. Katunuma, A. Ohashi, E. Sano, E. Murata, H. Shiota, K. Yamamoto, E. Majima and Q. T. Le: New cysteine protease inhibitors in physiological secretory fluids and their medical significances. Advances in Enzyme Regulation 43, 393-410 (2003)
30) Sakurai J, Nagahama M, Hisatsune J, Katunuma N, Tsuge H.: Clostridium perfringens iota-toxin, ADP-ribosyltransferase: structure and mechanism of action. Advances in Enzyme Regulation 43, 361-377 (2003)
31) Bervar A, Zajc I, Sever N, Katunuma N, Sloane BF, Lah TT.: Invasiveness of transformed human breast epithelial cell lines is related to cathepsin B and inhibited by cysteine proteinase inhibitors. Biol Chem. 384(3), 447-455 (2003)
32) Nobuhiko Katunuma, Yoichi Matsunaga, Kunisuke Himeno and Yoshio Hayashi: Insights into the roles of cathepsins in antigen processing and presentation revealed by specific inhibitors. Biol. Chem. 384, 883-890 (2003) Mini-review
33) Nobuhiko Katunuma, Hiroshi Shiota, and Quang Trong Le: Medical significance of cysteine protease inhibitors in mammalian secretory fluids. The Journal of Medical Investigation (JMI) 50(3, 4), 154-161 (2003) Review
34) N. Katunuma, H. Tsuge, M. Nukatsuka, M. Fukushima: Structure-based development of cathepsin L inhibitors and therapeutic applications for prevention of cancer metastasis and cancer-induced osteoporosis. Advances in Enzyme Regulation 42, 159-172 (2002)
35) N. Katunuma, H. Tsuge, M. Nukatsuka, T. Asao and M. Fukushima: Structure-based design of specific cathepsin inhibitors and their application to protection of bone metastasis of cancer cells. Archives of Biochemistry and Biophysics (ABB) Mini-review, 397(2), 305-311 (2002)
36) Kaoru Saegusa, Naozumi Ishimaru, Kumiko Yanagi, Rieko Arakaki, Kouichi Ogawa, Ichiro Saito, Nobuhiko Katunuma, and Yoshio Hayashi: Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity. The Journal of Clinical Investigation (J. Clin. Invest.), 110(3), 361-369 (2002)
37) Takeshi Nikawa, Madoka Ikemoto, Chiho Watanabe, Takako Kitano, Mihoko Kano, Makoto Yoshimoto, Takae Towatari, Nobuhiko Katunuma, Fujiko Shizuka and Kyoichi Kishi: A cysteine protease inhibitor prevents suspension-induced declines in bone weight and strength in rats. Journal of Physiological Anthropology, 21, 51-57 (2002)
38) Tsuyoshi Nishioku, Koichi Hashimoto, Keizo Yamashita, Shyh-Yuh Liou, Yoshifumi Kagamiishi, Hitoshi Maegawa, Nobuo Katsube, Christoph Peters, Kurt von Figura, Paul Saftig, Nobuhiko Katunuma, Kenji Yamamoto, and Hiroshi Nakanishi: Involvement of cathepsin E in exogenous antigen processing in primary cultured murine microglia. The Journal of Biological Chemistry, 277(7), 4816-4822 (2002)
39) Kazunari Yoneda, Tomohiro Nishimura, Nobuhiko Katunuma, Shigeyuki Imamura, Katsutoshi Nitta and Hideaki Tsuge: Crystallization and preliminary X-ray crystallographic studies of monoacylglycerol lipase of the moderately thermophilic Bacillus sp. H-257. Acta Cryst. (Biological Crystallography) D58, 1232-1233 (2002)
40) Motohiro Kihara, Hisao Kakegawa, Yuko Matano, Etsuko Murata, Hideaki Tsuge, Hiroshi Kido and Nobuhiko Katunuma: Chondroitin Sulfate Proteoglycan Is a Potent Enhancer in the Processing of Procathepsin L. Biological Chemistry. 383, 1925-1929 (2002)
41) Hideaki Tsuge, Haruhiko Sakuraba, Toru Kobe, Akira Kujime, Nobuhiko Katunuma, and Toshihisa Ohshima: Crystal structure of the ADP-dependent glucokinase form Pyrococcus horikoshiiat 2.0-A resolution: A large conformational change in ADP-dependent glucokinase. Protein Science, 11, 2456-2463 (2002)
42) N. Katunuma, A. Matsui, Q. T. Le, K. Utsumi, G. Salvesen and A. Ohashi: Novel procaspase-3 activating cascade mediated by lysoapoptases and its biological significances in apoptosis. Advances in Enzyme Regulation., 41, 237-250 (2001)
43) Sizuo Kitano, Kenji Irimura, Toru Sasaki, Naoko Abe, Atsuyo Baba, Yoichiro Miyake, Nobuhiko Katunuma and Kenji Yamamoto: Suppression of Gingival Inflammation Induced by Porphyromonas gingivalis in Rats by Leupeptin. Jpn. J. Pharmacol. 85, 84-91 (2001)
44) Tianqian Zhang, Yoichi Maekawa, Tohru Sakai, Yoko Nakano, Kazunari Ishii, Hajime Hisaeda, Eiki Kominami, Nobuhiko Katunuma, Tetsuji Asao, and Kunisuke Himeno: Splenic cathepsin L is Maturated from the proform by interferon-g after immunization with exogenous antigens. Biochemical and Biophysical Research Communications (BBRC), 283, 499-506 (2001)
45) Yoko Hashimoto, Hisao Kakegawa, Yasushi Narita, Yudo Hachiya, Taro Hayakawa, Janko Kos, Vito Turk, and Nobuhiko Katunuma: Significance of cathepsin B accumulation in synovial fluid of rheumatoid arthritis. BBRC, 283, 334-339 (2001)
46) Premzl A, Puizdar V, Zavasnik-Bergant V, Kopitar-Jerala N, Lah TT, Katunuma N, Sloane BF, Turk V, Kos J.: Invasion of ras-transformed breast epithelial cells depends on the proteolytic activity of cysteine and aspartic proteinases. Biol Chem. 382(5), 853-857 (2001)
47) Zhang T, Maekawa Y, Sakai T, Nakano Y, Ishii K, Hisaeda H, Dainichi T, Asao T, Katunuma N, Himeno K.:
Treatment with cathepsin L inhibitor potentiates Th2-type immune response in Leishmania major-infected BALB/c mice.
Int Immunol. 13, 975-982 (2001)

最近5年間の和文リスト
1) 勝沼信彦：アトモスフィア“タンパク質分解の研究に花が咲いた”『生化学』第77巻、4号、305 (2005)
2) 片山智子、齋藤晴比古、塩田洋、勝沼信彦：“涙液中の特殊蛋白検出によるベーチェット病、原田病の診断”『特集　平成15年度高度医療研究』第57巻3号、203-204 (2005)
3) 勝沼信彦：ビタミンの必要量を再考する；ビタミン77巻2号、69-73 (2003)
4) 勝沼信彦：巻頭言“ﾌﾟﾛﾃｱｰｾﾞ，ﾌﾟﾛﾃｱｰｾﾞ･ｲﾝﾋﾋﾞﾀｰの医学的位置付け”『臨床検査』47巻8号、831-832（2003）医学書院
5) 勝沼信彦：“ﾌﾟﾛﾃｱｰｾﾞ･ｲﾝﾋﾋﾞﾀｰの新検出法　Reverse Zymography”『臨床検査』47巻8号、871-874（2003）医学書院
6) 木戸博、勝沼信彦：膵臓トリプシンインヒビター—Kunitz型(塩基性)、Kazal型(分泌性)；制御タンパク質　大和和雄・編集　廣川タンパク質化学第7巻、頁1-5（2002）
7) 勝沼信彦：リソゾーム・システインプロテアーゼインヒビター群・シスタチン類；制御タンパク質　大和和雄・編集　廣川タンパク質化学第7巻、頁6-13（2002）
8) 村田悦子、中野基裕、大橋敦、Le Trong Quang、山本正子、勝沼信彦：D-Galactosamine誘導肝細胞アポトーシスの発生分子機構とTea-catechinによる抑制；ビタミン76巻５・６号、頁283-289（2002）
9) 犬伏知子、勝沼信彦：マウスの糖利用および血清Insulinレベルに及ぼすビタミンＢ6の効果（Effects of Vitamin B6 on Glucose Utilization and Serum Insulin Level in Mice）；ビタミン76巻９号、頁403-411（2002)