Molecular analysis of epigenetic factors involved in the induction of spermatogenic cell apoptosis

• Project/Area Number: 18390060
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Nagasaki University
• Principal Investigator: KOJI Takehiko Nagasaki University, 大学院・医歯薬学総合研究科, 教授 (30170179)
• Co-Investigator(Kenkyū-buntansha): HISHIKAWA Yoshitaka 長崎大学, 大学院・医歯薬学総合研究科, 准教授 (60304276) ; IZUMI Shinichi 長崎大学, 大学院・医歯薬学総合研究科, 助教 (40264246) ; AN Shucai 長崎大学, 大学院・医歯薬学総合研究科, 助教 (30404213) ; SATO Yoko 長崎大学, 大学院・医歯薬学総合研究科, 助教 (50398963)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥16,480,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥1,980,000); Fiscal Year 2008: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2007: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2006: ¥7,900,000 (Direct Cost: ¥7,900,000)
• Keywords: 精子形成細胞 / DNAのメチル化 / 分子組織化学 / ヒストン蛋白修飾 / 免疫組織化学 / ヘテロクロマチン化 / アポトーシス / 初代培養

Research Abstract

雄性生殖細胞を生み出す精子形成過程では、精子換算で約25-75%の生殖細胞が失われることに注目し、この自発的細胞死の誘導機構を解析した。特に本過程がDNAからなるクロマチンの規則的な凝集過程であり、その調節破綻が自殺死誘導の原因ではないかと考え、クロマチン凝集に深く関与するDNAのメチル化を独自に開発したHELMET法により解析し、死を誘導された細胞核では顕著にDNAの非メチル化が生じていることを初めて明らかにした。

Research Products

• [Journal Article] Keratinocyte growth factor accelerates compensatory growth in the remaining lung after trilobectomy in rats (2009)
  • Author(s): Matsumoto K, Nagayasu T, Hishikawa Y, Tagawa T, Yamayoshi T, Abo T, Tobinaga S, Furukawa K, Koji T
  • Journal Title: J Thorac Cardiovasc Surg 137(in press)
  • NAID: 120006984032
  • Peer Reviewed
• [Journal Article] Keratinocyte growth factor accelerates compensatory growth in the remaining lung after trilobectomy in rats. (2009)
  • Author(s): Matsumoto, K.
  • Journal Title: J. Thorac. Cardiovasc. Surg. 137(in press)
  • Peer Reviewed
• [Journal Article] In situ detection of methylated DNA by histo endonuclease-linked detection of methylated DNA sites : a new principle of analysis of DNA methylation (2008)
  • Author(s): Koji T, Kondo S, Hishikawa Y, An S, Sato Y
  • Journal Title: Histochem Cell Biol 130 Pages: 917-925
  • NAID: 120006984031
  • Peer Reviewed
• [Journal Article] Deubiquitylation of histone H2A activates transcriptional initiation viatrans-histone cross-talk with H3K4 di-and trimethylation (2008)
  • Author(s): Nakagawa T, Kajitani T, Togo S, Masuko N, Ohdan H, Hishikawa Y, Koji T, Matsuyama T, Ikura T, Muramatsu M, Ito T
  • Journal Title: Genes Dev 22 Pages: 37-49
  • Peer Reviewed
• [Journal Article] Suppression of Renal Tubulointerstitial Fibrosis by Small Interfering RNA Targeting Heat Shock Protein 47 (2008)
  • Author(s): Xia Z, Abe K, Furusu A, Miyazaki M, Obata Y, Tabata Y, Koji T, Kohno S
  • Journal Title: Am J Nephrol 28 Pages: 34-46
  • Peer Reviewed
• [Journal Article] Regeneration of peritoneal mesothelium in a rat model of peritoneal fibrosis (2008)
  • Author(s): Nishioka Y, Miyazaki M, Abe K, Furusu A, Harada T, Ozono Y, Taguchi T, Koji T, Kohno S
  • Journal Title: Ren Fail 30 Pages: 97-105
  • NAID: 120006984551
  • Peer Reviewed
• [Journal Article] Topical application of 5-fluorouracil on attic cholesteatoma results in downregulation of keratinocyte growth factor and reduction of proliferative activity (2008)
  • Author(s): Yamamoto-Fukuda T, Terakado M, Hishikawa Y, Koji T, Takahashi H
  • Journal Title: Eur Arch Otorhinolaryngol 265 Pages: 1173-1178
  • NAID: 120006983530
  • Peer Reviewed
• [Journal Article] Involvement of bone marrow-derived endothelial progenitor cells in glomerular capillary repair in habu snake venom-induced glomerulonephritis (2008)
  • Author(s): Abe-Yoshio Y, Abe K, Miyazaki M, Furusu A, Nishino T, Harada T, Koji T, Kohno S
  • Journal Title: Virchows Arch 453 Pages: 97-106
  • Peer Reviewed
• [Journal Article] Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver (2008)
  • Author(s): Nakajima H, Mizuta N, Fujiwara I, Sakaguchi K, Ogata H, Magae J, Yagita H, Koji T
  • Journal Title: Apoptosis 13 Pages: 1013-1021
  • Peer Reviewed
• [Journal Article] Rapid and significant induction of TRAIL-mediated type II cells in apoptosis of primary salivary epithelial cells in primary Sjogren's syndrome (2008)
  • Author(s): Nakamura H, Kawakami A, Iwamoto N, Ida H, Koji T, Eguchi K
  • Journal Title: Apoptosis 13 Pages: 1322-1330
  • NAID: 120006983760
  • Peer Reviewed
• [Journal Article] Renoprotective effect of azelnidipine in rats (2008)
  • Author(s): Kurashige T, Abe K, Furusu A, Miyazaki M, Obata Y, Xia Z, Nakazawa M, Nakazawa Y, Funakoshi S, Harada T, Koji T, Kohno S
  • Journal Title: Biol Pharm Bull 31 Pages: 2237-2244
  • NAID: 110007005022
  • Peer Reviewed
• [Journal Article] Adhesion-dependent growth of primary adult T cell leukemia cells with down-regulation of HTLV-I p40Tax protein : a novel in vitro model of the growth of acute ATL cells (2008)
  • Author(s): Nagai K, Jinnai I, Hata T, Usui T, Sasaki D, Tsukasaki K, Sugahara K, Hishikawa Y, Yamada Y, Tanaka Y, Koji T, Mano H, Kamihira S, Tomonaga M
  • Journal Title: Int J Hematol 88 Pages: 551-564
  • NAID: 10023971331
  • Peer Reviewed
• [Journal Article] In situ detection of methylated DNA by histo endonuclease-linked detection of methylated DNA sites : a new principle of analysis of DNA methylation. (2008)
  • Author(s): Koji, T.
  • Journal Title: Histochem. Cell Biol. 130 Pages: 917-925
  • NAID: 120006984031
  • Peer Reviewed
• [Journal Article] Deubiquityiation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation. (2008)
  • Author(s): Nakagawa, T.
  • Journal Title: Genes. Dev. 22 Pages: 37-49
  • Peer Reviewed
• [Journal Article] Suppression of Renal Tubulointerstitial Fibrosis by Small Interfering RNA Targeting Heat Shock Protein 47. (2008)
  • Author(s): Xia, Z.
  • Journal Title: Am. J. Nephrol. 28 Pages: 34-46
  • Peer Reviewed
• [Journal Article] Regeneration of peritoneal mesothelium in a rat model of peritoneal fibrosis. (2008)
  • Author(s): Nishioka, Y.
  • Journal Title: Ren. Fail. 30 Pages: 97-105
  • Peer Reviewed
• [Journal Article] Topical application of 5-fluorouracil on attic cholesteatoma results in downregulation of keratinocyte growth factor and reduction of proliferative activity. (2008)
  • Author(s): Yamamoto-Fukuda, T.
  • Journal Title: Eur. Arch. Otorhinolaryngol. 265 Pages: 1173-1178
  • Peer Reviewed
• [Journal Article] Involvement of bone marrow-derived endothelial progenitor cells in glomerular capillary repair in habu snake venom-induced glomerulonephritis. (2008)
  • Author(s): Abe-Yoshio, Y.
  • Journal Title: Virchows Arch. 453 Pages: 97-106
  • Peer Reviewed
• [Journal Article] Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver. (2008)
  • Author(s): Nakajima, H.
  • Journal Title: Apoptosis 13 Pages: 1013-1021
  • Peer Reviewed
• [Journal Article] Rapid and significant induction of TRAIL-mediated type II cells in apoptosis of primary salivary epithelial cells in primary Sjogren's syndrome. (2008)
  • Author(s): Nakamura, H.
  • Journal Title: Apoptosis 13 Pages: 1322-1330
  • Peer Reviewed
• [Journal Article] Renoprotective effect of azelnidipine in rats. (2008)
  • Author(s): Kurashige, T.
  • Journal Title: Biol. Pharm. Bull. 31 Pages: 2237-2244
  • Peer Reviewed
• [Journal Article] Adhesion-dependent growth of primary adult T cell leukemia cells with down-regulation of HTLV-Ip40Tax protein : a novel in vitro model of the growth of acute ATL cells. (2008)
  • Author(s): Nagai, K.
  • Journal Title: Int. J. Hematol. 88 Pages: 551-564
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of connexin43 expression in infertile human testes (2007)
  • Author(s): Matsuo Y, Nomata K, Eguchi J, Aoki D, Hayashi T, Hishikawa Y, Kanetake H, Shibata Y, Koji T
  • Journal Title: Acta Histochem Cytochem 40 Pages: 69-75
  • NAID: 110006633416
  • Peer Reviewed
• [Journal Article] Hyperthyroidism induces apoptosis in rat liver through activation of death receptor-mediated pathways (2007)
  • Author(s): Kumar A, Sinha RA, Tiwari M, Singh R, Koji T, Manhas N, Rastogi L, Pal L, Shrivastava A, Sahu RP, Godbole MM
  • Journal Title: J Hepatol 46 Pages: 888-898
  • Peer Reviewed
• [Journal Article] Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar(Burma) (2007)
  • Author(s): Kyaw Soe, Hishikawa Y, Fukuzawa Y, Win N, Yin KS, Win KM, Myint AA, Koji T
  • Journal Title: J Gastroenterol 42 Pages: 225-235
  • Peer Reviewed
• [Journal Article] The expression of vascular dendritic cells in human atherosclerotic carotid plaques (2007)
  • Author(s): Kawahara I, Kitagawa N, Tsutsumi K, Nagata I, Hayashi T, Koji T
  • Journal Title: Hum Pathol 38 Pages: 1378-1385
  • Peer Reviewed
• [Journal Article] Lung injury after ischemia-reperfusion of small intestine in rats involves apoptosis of type II alveolar epithelial cells mediated by TNF-alpha and activation of Bid pathway (2007)
  • Author(s): An S, Hishikawa Y, Liu J, Koji T
  • Journal Title: Apoptosis 12 Pages: 1989-2001
  • Peer Reviewed
• [Journal Article] Epidermal growth factor inhibits Fas-mediated apoptosis in salivary epithelial cells of patients with primary Sjogren's syndrome (2007)
  • Author(s): Nakamura H, Kawakami A, Ida H, Koji T, Eguchi K
  • Journal Title: Clin Exp Rheumatol 25 Pages: 831-837
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of connexin43 expression in infertile human testes. (2007)
  • Author(s): Matsuo, Y.
  • Journal Title: Acta Histochem.Cytochem. 40 Pages: 69-75
  • Peer Reviewed
• [Journal Article] Hyperthyroidism induces apoptosis in rat liver through activation of death receptor-mediated pathways. (2007)
  • Author(s): Kumar, A.
  • Journal Title: J. Hepatol. 46 Pages: 888-898
  • Peer Reviewed
• [Journal Article] Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar(Burma). (2007)
  • Author(s): Kyaw Soe
  • Journal Title: J. Gastroenterol. 42 Pages: 225-235
  • Peer Reviewed
• [Journal Article] The expression of vascular dendritic cells in human atherosclerotic carotid plaques. (2007)
  • Author(s): Kawahara, I.
  • Journal Title: Hum.Pathol. 38 Pages: 1378-1385
  • Peer Reviewed
• [Journal Article] Lung injury after ischemia-reperfusion of small intestine in rats involves apoptosis of type II alveolar epithelial cells mediated by TNF-alpha and activation of Bid pathway. (2007)
  • Author(s): An, S.
  • Journal Title: Apoptosis 12 Pages: 1989-2001
  • Peer Reviewed
• [Journal Article] Epidermal growth factor inhibits Fas-mediated apoptosis in salivary epithelial cells of patients with primary Sjogren's syndrome. (2007)
  • Author(s): Nakamura, H.
  • Journal Title: Clin.Exp.Rheumatol. 25 Pages: 831-837
  • Peer Reviewed
• [Journal Article] Diethylstilbestrol increases the density of prolactin cells in male mouse pituitary by inducing proliferation of prolactin cells and transdifferentiation of gonadotropic cells (2006)
  • Author(s): Shukuwa K, Izumi S, Hishikawa Y, Ejima K, Inoue S, Muramatsu M, Ouchi Y, Kitaoka T, Koji T
  • Journal Title: Histochem Cell Biol 126 Pages: 111-123
• [Journal Article] Identification of estrogen receptor beta-positive intraepithelial lymphocytes and their possible roles in normal and tubal pregnancy oviducts (2006)
  • Author(s): Ulziibat S, Ejima K, Shibata Y, Hishikawa Y, Kitajima M, Fujishita A, Ishimaru T, Koji T
  • Journal Title: Hum Reprod 21 Pages: 2281-2289
  • Peer Reviewed
• [Journal Article] Expression of the Snurf-Snrpn IC transcript in the oocyte and its putative role in the imprinting establishment of the mouse 7C imprinting domain (2006)
  • Author(s): Mapendano CK, Kishino T, Miyazaki K, Kondo S, Yoshiura K, Hishikawa Y, Koji T, Niikawa N, Ohta T
  • Journal Title: J Hum Genet 51 Pages: 236-243
  • NAID: 10018115776
  • Peer Reviewed
• [Journal Article] Gene transfer using nonviral delivery system (2006)
  • Author(s): Miyazaki M, Obata Y, Abe K, Furusu A, Koji T, Tabata Y, Kohno S
  • Journal Title: Perit Dial Int 26 Pages: 633-640
  • Peer Reviewed
• [Journal Article] 17Beta-estradiol protects against oxidative stress-induced cell death through the glutathione/glutaredoxin-dependent redox regulation of Akt in myocardiac H9c2 cells (2006)
  • Author(s): Urata Y, Ihara Y, Murata H, Goto S, Koji T, Yodoi J, Inoue S, Kondo T
  • Journal Title: J Biol Chem 281 Pages: 13092-13102
  • Peer Reviewed
• [Journal Article] A novel alternative splicing isoform of human T-cell leukemia virus type 1 bZIP factor(HBZ-SI)targets distinct subnuclear localization (2006)
  • Author(s): Murata K, Hayashibara T, Sugahara K, Uemura A, Yamaguchi T, Harasawa H, Hasegawa H, Tsuruda K, Okazaki T, Koji T, Miyanishi T, Yamada Y, Kamihira S
  • Journal Title: J Virol 80 Pages: 2495-2505
  • Peer Reviewed
• [Journal Article] Diethylstilbestrol increases the density of prolactin cells in male mouse pitulitary by inducing proliferation of prolactin cells and transdifferentiation of gonadotropic cells. (2006)
  • Author(s): Shukuwa, K.
  • Journal Title: Histochem.Cell Biol. 126・1 Pages: 111-123
• [Journal Article] Identification of estrogen receptor beta-positive intraepithelial lymphocytes and their possible roles in normal and tubal pregnancy oviducts. (2006)
  • Author(s): Ulziibat, S.
  • Journal Title: Hum.Reprod. 21・9 Pages: 2281-2289
• [Journal Article] Expression of the Snurf-Snrpn IC transcript in the oocyte and its putatie role in the imprinting establishment of the mouse 7C imprinting domain. (2006)
  • Author(s): Mapendano, C.K.
  • Journal Title: J.Hum.Genet. 51・3 Pages: 236-243
• [Journal Article] Gene Transfer using nonviral delivery systems. (2006)
  • Author(s): Miyazaki, M.
  • Journal Title: Perit Dial.Int. 26・6 Pages: 633-640
• [Journal Article] 17Beta-estradiol protects against oxidative stress-induced cell death through the glutathione/glutaredoxin-dependent redox regulation of Akt in myocardiac H9c2 cells. (2006)
  • Author(s): Urata, Y.
  • Journal Title: J.Boil.Chem. 281・19 Pages: 13092-13102
• [Journal Article] A novel alternative splicing isoform of human T-cell leukemia virus type 1 bZIP factor(HBZ-SI)targets distinct subnuclear localization. (2006)
  • Author(s): Murata, K.
  • Journal Title: J.Virol. 80・5 Pages: 2495-2505
• [Presentation] マウス精巣細胞での核小体に於けるリボソーム遺伝子転写産物動態 (2008)
  • Author(s): 小路武彦
  • Organizer: 第49回日本組織化学会総会・学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2008-10-05
• [Presentation] マウス精巣細胞での核小体に於けるリボソーム遺伝子転写産物動態。 (2008)
  • Author(s): 小路武彦
  • Organizer: 第49回日本組織化学会総会・学術集会
  • Place of Presentation: 長崎県長崎市
  • Year and Date: 2008-10-05
• [Presentation] Updated non-radioactive in situ hybridization in cell biology and physiology (2008)
  • Author(s): Koji T
  • Organizer: XIII International Congress of Histochemistry and Cytochemistry
  • Place of Presentation: Gdansk, Poland
  • Year and Date: 2008-08-24
• [Presentation] Updated non-radioactive in situ hybridization in cell biology and physiology. (2008)
  • Author(s): Koji, T.
  • Organizer: XIII International Congress of Histochemistry and Cytochemistry
  • Place of Presentation: Gdansk, Poland
  • Year and Date: 2008-08-24
• [Presentation] 生殖細胞アポトーシスに於けるミトコンドリア動態変化とERβ発現の関与 (2008)
  • Author(s): 菱川善隆・小路武彦
  • Organizer: 第17回日本アポトーシス研究会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-08-01
• [Presentation] 生殖細胞アポトーシスに於けるミトコンドリア動態変化とERβ発現の関与。 (2008)
  • Author(s): 菱川善隆
  • Organizer: 第17回日本アポトーシス研究会学術集会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2008-08-01
• [Presentation] 生殖細胞アポトーシスとミトコンドリア動態 (2008)
  • Author(s): 菱川善隆・小路武彦
  • Organizer: 第113回日本解剖学会総会・全国学術集会
  • Place of Presentation: 大分
  • Year and Date: 2008-03-29
• [Presentation] 電子顕微鏡レベルでのin situ hybridizationによる核小体に於けるpre-rRNAの局在 (2008)
  • Author(s): 小路武彦
  • Organizer: 第113回日本解剖学会総会・全国学術集会
  • Place of Presentation: 大分
  • Year and Date: 2008-03-27
• [Presentation] 精子形成過程に於けるヒストン修飾解析とDNAメチル化部位局在化法 (2007)
  • Author(s): 小路武彦
  • Organizer: 第48回日本組織細胞化学会総会・学術集会
  • Place of Presentation: 甲府
  • Year and Date: 2007-09-28
• [Presentation] 精子形成過程に於けるヒストン修飾解析とDNAメチル化部位局在化法 (2007)
  • Author(s): 小路 武彦
  • Organizer: 第48回に本組織細胞化学会
  • Place of Presentation: 山梨県甲府市
  • Year and Date: 2007-09-28
• [Book] 永遠の不死 ; 精子形成細胞の生物学 (2009)
  • Author(s): 小路武彦(編著)
  • Total Pages: 143
  • Publisher: サイエンス社
• [Book] 永遠の不死 ; 精子形成細胞の生物学 (2009)
  • Author(s): 小路武彦
  • Total Pages: 143
  • Publisher: サイエンス社
• [Book] In situ ハイブリダイゼーションの基礎と応用。[組織細胞化学2008](日本組織細胞化学会編) (2008)
  • Author(s): 菱川善隆・小路武彦
  • Publisher: 中西印刷
• [Book] [組織細胞化学2007](日本組織細胞化学会編)In situハイブリダイゼーションの基礎と応用 (2008)
  • Author(s): 菱川善隆
  • Total Pages: 15
  • Publisher: 中西印刷
• [Book] ヒトの発生・遺伝・老化。[ビジュアル解剖生理学](藤本淳監修、藤田守、土肥良秋編) (2007)
  • Author(s): 小路武彦・江島邦彰・菱川善隆
  • Publisher: ヌーヴェルヒロカワ
• [Book] In situ ハイブリダイゼーション法の基礎と応用。[組織細胞化学2007](日本組織細胞化学会編) (2007)
  • Author(s): 小路武彦
  • Publisher: 学際企画
• [Book] [組織細胞化学2007] (日本組織細胞化学会編) In situ ハイブリダイゼーション法の基礎と応用。 (2007)
  • Author(s): 小路 武彦
  • Total Pages: 11
  • Publisher: 学際企画
• [Book] [ビジュアル解剖生理学] (藤本淳監修、藤田守・土肥良秋編) 第12章 ヒトの発生・遺伝・老化。 (2007)
  • Author(s): 小路 武彦
  • Total Pages: 17
  • Publisher: ヌーヴェルヒロカワ
• [Book] 特異的RNA分子の発現をみる-利用可能な方法の比較-。[実験医学別冊染色・バイオイメージング実験ハンドブック](高田邦昭、斉藤尚亮、川上速人編) (2006)
  • Author(s): 小路武彦
  • Publisher: 羊土社
• [Book] 特異的RMA分子の発現をみる-利用可能な方法の比較-実験医学別冊 染色・バイトイメージング実験ハンドブック(高田邦昭, 斉藤尚亮, 川上速人(編)) (2006)
  • Author(s): 小路武彦
  • Publisher: 羊土社
• [Patent(Industrial Property Rights)] DNAメチル化部位の局在検出方法 (2008)
  • Inventor(s): 小路武彦・近藤志穂
  • Industrial Property Rights Holder: 小路武彦・近藤志穂
  • Industrial Property Number: 2008-241679
  • Filing Date: 2008-09-19
• [Patent(Industrial Property Rights)] DNAメチル化部位の局在検出方法 (2008)
  • Inventor(s): 小路武彦
  • Industrial Property Rights Holder: 小路武彦
  • Industrial Property Number: 2008-241679
  • Filing Date: 2008-09-19