Analysis of erythroid differentiation by HSP27

• Project/Area Number: 23570172
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Keio University
• Principal Investigator: KABE Yasuaki 慶應義塾大学, 医学部, 講師 (20397037)
• Co-Investigator(Renkei-kenkyūsha): ISHIMORI Koichiro 北海道大学, 理学部, 教授 (20192487)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ヘム / 赤血球分化 / 金属タンパク質 / アポトーシス

Research Abstract

During erythropoiesis, haem synthesis is significantly induced, and abundant haem is utilized as hemoglobin in erythroid cells. However, excessive haem results in cell damages by membrane oxidation. In the present study, we found that haem directly bound to heat shock protein 27 (HSP27) by affinity purification. HSP27 is a small heat shock family protein, which plays an important role for cytoprotection, stress tolerance, cellular differentiation or tissue development. It has been known that the multimerized HSP27 dissociates by several stimuli. Interestingly, exposure of haem directly dissociated the multimerized HSP27 in vivo and in vitro. Knockdown of HSP27 expression resulted in the haem-induced apoptosis and reduced the haemin-induced erythroid differentiation. Furthermore, we also found that HSP27 is essential for erythroid differentiation by using HSP27 knockdown mice.

Research Products

• [Journal Article] Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts. (2014)
  • Author(s): Toue S, Sugiura Y, Kubo A, Ohmura M, Karakawa S, Mizukoshi T, Yoneda J, Miyano H, Noguchi Y, Kobayshi T, Kabe Y, Suematsu M.
  • Journal Title: Proteomics Volume: 14 Issue: 7-8 Pages: 810-819
  • DOI: 10.1002/pmic.201300041
  • Peer Reviewed
• [Journal Article] Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts (2013)
  • Author(s): Toue S, Sugiura Y, Kubo A, Ohmura M, Karakawa S, Mizukoshi T, Yoneda J, Miyano H, Noguchi Y, Kobayshi T, Kabe Y, Suematsu M.
  • Journal Title: Proteomics Volume: 14(7-8) Pages: 810-9
  • Peer Reviewed
• [Journal Article] Vesnarinone suppresses TNFαmRNA expression by inhibiting valosin-containing protein (2013)
  • Author(s): Hotta K, Nashimoto A, Yasumura E, Suzuki M, Azuma M, Iizumi Y, Shima D, Nabeshima R, Hiramoto M, Okada A, Sakata-Sogawa K, Tokunaga M, Ito T, Ando H, Sakamoto S, Kabe Y, Aizawa S, Imai T, Yamaguchi Y, Watanabe H, Handa H.
  • Journal Title: Mol Pharmacol Volume: 83(5) Pages: 930-8
  • Peer Reviewed
• [Journal Article] Vitamin K2 covalently binds to Bak and induces Bak-mediated apoptosis (2013)
  • Author(s): Karasawa S, Azuma M, Kasama T, Sakamoto S, Kabe Y, Imai T, Yamaguchi Y, Miyazawa K, Handa H.
  • Journal Title: Mol Pharmacol Volume: 83(3) Pages: 613-20
  • Peer Reviewed
• [Journal Article] Vesnarinone Suppresses TNF α mRNA Expression by Inhibiting Valosin-containing Protein (2013)
  • Author(s): Hotta K, Nashimoto A, Yasumura E, Suzuki M, Azuma M, Iizumi Y, Shima D, Nabeshima R, Hiramoto M, Okada A, Sakata-Sogawa K, Tokunaga M, Ito T, Ando H, Sakamoto S, Kabe Y, Aizawa S, Imai T, Yamaguchi Y, Watanabe H, Handa H
  • Journal Title: Mol Pharmacol Volume: Vol.83 Issue: 5 Pages: 930-938
  • DOI: 10.1124/mol.112.081935
  • Peer Reviewed
• [Journal Article] Vitamin K2 covalently binds to Bak and induces Bak-mediated apoptosis. (2013)
  • Author(s): Karasawa S, Azuma M, Kasama T, Sakamoto S, Kabe Y, Imai T, Yamaguchi Y, Miyazawa K, Handa H
  • Journal Title: Mol Pharmacol Volume: 83 Issue: 3 Pages: 613-620
  • DOI: 10.1124/mol.112.082602
  • Peer Reviewed
• [Journal Article] Microscopic imaging mass spectrometry assisted by on-tissue chemical derivatization for visualizing multiple amino acids in human colon cancer xenografts (2013)
  • Author(s): Toue S, Sugiura Y, Kubo A, Ohmura M, Karasawa S, Mizukoshi M, Yoneda J, MIyano H, Noguchi Y, KObayashi T, Kabe Y, Suematsu M
  • Journal Title: Proteomics Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Vesnarinone Suppresses TNFα mRNA Expression by Inhibiting Valosin-containing Protein. (2013)
  • Author(s): Hotta K, Nashimoto A, Yasumura E, Suzuki M, Azuma M, Iizumi Y, Shima D, Ando H, Sakamoto S, Kabe Y, Aizawa S, Imai T, Yamaguchi Y, Watanabe H, Handa H.
  • Journal Title: Mol Pharmacol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Involvement of NF-κB-mediated expression of galectin-3-binding protein in TNF-α-induced breast cancer cell adhesion (2012)
  • Author(s): Noma N, Simizu S, Kambayashi Y, Kabe Y, Suematsu M, Umezawa K.
  • Journal Title: Oncol Rep Volume: 27(6) Pages: 2080-4
  • Peer Reviewed
• [Journal Article] Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway (2012)
  • Author(s): Morikawa T, Kajimura M, Nakamura T, Hishiki T, Nakanishi T, Yukutake Y, Nagahata Y, Ishikawa M, Hattori K, Takenouchi T, Takahashi T, Ishii I, Matsubara K, Kabe Y, Uchiyama S, Nagata E, Gadalla MM, Snyder SH, Suematsu M.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109(4) Pages: 1293-8
  • Peer Reviewed
• [Journal Article] HIF-1αinduction suppresses excessive lipid accumulation in alcoholic fatty liver in mice (2012)
  • Author(s): Nishiyama Y, Goda N, Kanai M, Niwa D, Osanai K, Yamamoto Y, Senoo-Matsuda N, Johnson RS, Miura S, Kabe Y, Suematsu M.
  • Journal Title: J Hepatol. Volume: 56(2) Pages: 441-7
  • Peer Reviewed
• [Journal Article] Involvement of NF-κB-mediated expression of galectin-3-binding protein in TNF-α-induced breast cancer cell adhesion. (2012)
  • Author(s): Noma N, Simizu S, Kambayashi Y, Kabe Y, Suematsu M, Umezawa K.
  • Journal Title: Oncol Rep. Volume: 27 Pages: 2080-2084
  • Peer Reviewed
• [Journal Article] Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway. (2012)
  • Author(s): Morikawa T, Kajimura M, Nakamura T, Hishiki T,Ishikawa M, Hattori K, Takenouchi T, Takahashi T, Ishii I, Matsubara K, Kabe Y, Uchiyama S, Nagata E, Gadalla MM, Snyder SH, Suematsu M.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 109 Pages: 1293-1298
  • Peer Reviewed
• [Journal Article] HIF-1α induction suppresses excessive lipid accumulation in alcoholic fatty liver in mice. (2012)
  • Author(s): Nishiyama Y, Goda N, Kanai M, Niwa D, Osanai K, Yamamoto Y, Senoo-Matsuda N, Johnson RS, Miura S, Kabe Y, Suematsu M.
  • Journal Title: J Hepatol. Volume: 56 Pages: 441-447
  • Peer Reviewed
• [Journal Article] Involvement of NF-κB-mediated expression of galectin-3-binding protein in TNF-α-induced breast cancer cell adhesion. (2012)
  • Author(s): Noma N, Simizu S, Kambayashi Y, Kabe Y, Suematsu M, Umezawa K
  • Journal Title: Oncology Reports Volume: 27 Pages: 2080-2084
  • URL: http://www.spandidos-publications.com/serveFile/or_27_6_2080_PDF.pdf?type=article&article_id=or_27_6_2080&item=PDF
  • Peer Reviewed
• [Journal Article] Identification of dynamin-2-mediated endocytosis as a new target of osteoporosis drugs, bisphosphonates (2011)
  • Author(s): Masaike Y, Takagi T, Hirota M, Yamada J, Ishihara S, Yung TM, Inoue T, Sawa C, Sagara H, Sakamoto S, Kabe Y, Takahashi Y, Yamaguchi Y, Handa H.
  • Journal Title: Mol Pharmacol. Volume: 77(2) Pages: 262-9
  • Peer Reviewed
• [Journal Article] Gas Biology Research in Clinical Practice : Roles of Stress-Inducible Carbon Monoxide in the Regulation of Liver Function (2011)
  • Author(s): Suematsu M, Kajimura M, Kabe Y.
  • Journal Title: KARGAR press Pages: 1-5
• [Journal Article] Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway. (2011)
  • Author(s): Morikawa T, Kajimura M, Nakamura T, Kabe Y, et al
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 109 Pages: 1293-1298
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268316/pdf/pnas.201119658.pdf
  • Peer Reviewed
• [Journal Article] HIF-1α induction suppresses excessive lipid accumulation in alcoholic fatty liver in mice. (2011)
  • Author(s): Nishiyama Y, Goda N, Kanai M, Niwa D, Osanai K, Yamamoto Y, Senoo-Matsuda N, Johnson RS, Miura S, Kabe Y, Suematsu M.
  • Journal Title: Journal of Hepatology Volume: 56 Pages: 441-447
  • Peer Reviewed
• [Presentation] 新規 CO ガス受容体を介した肝障害制御機構の解明 (2014)
  • Author(s): 加部泰明
  • Organizer: 第12回分子予防環境医学研究会
  • Place of Presentation: つくばサイエンス・インフォメーションセンター
  • Invited
• [Presentation] 新規COガス受容体を介した肝障害制御機構の解明 (2013)
  • Author(s): 加部泰明
  • Organizer: 第12回分子予防環境医学研究会
  • Place of Presentation: つくばサイエンス・インフォメーションセンター
  • Year and Date: 2013-02-01
  • Invited
• [Presentation] ヘム/COによるGAPDHを介した細胞防御機構の解明 (2012)
  • Author(s): 加部泰明, 末松誠
  • Organizer: 第35回日本分子生物学会年回
  • Place of Presentation: 福岡国際会議場 (口頭・ポスター発表)
  • Year and Date: 2012-12-13
• [Presentation] Regulation of the GAPDH-mediated cell death by CO gas (2012)
  • Author(s): 加部泰明、半田宏、末松誠
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
• [Presentation] COガスによる細胞防御機構の解明 (2011)
  • Author(s): 加部泰明, 末松誠
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜 (口頭・ポスター発表)
  • Year and Date: 2011-12-15
• [Presentation] ガス分子応答性受容体の系統的探索と機能解明 (2011)
  • Author(s): 加部泰明, 末松誠
  • Organizer: 第64回日本酸化ストレス学会
  • Place of Presentation: 北海道ルスツリゾートホテル&コンベンション (口頭発表)
  • Year and Date: 2011-07-03
• [Presentation] ヘム/COによるGAPDHを介した細胞防御機構の解明 (2011)
  • Author(s): 加部泰明, 末松誠
  • Organizer: 第38回生体分子科学討論会
  • Place of Presentation: 筑波大学大学会館国際会議室 口頭発表)
  • Year and Date: 2011-06-23
• [Presentation] ヘム/COによる細胞防御機構の解明 (2011)
  • Author(s): 加部泰明, 末松誠
  • Organizer: 第32回日本炎症・再生医学会
  • Place of Presentation: 国立京都国際会館 口頭発表)
  • Year and Date: 2011-06-03
• [Presentation] ヘム/COによるGAPDHを介した細胞防御機構の解明 (2011)
  • Author(s): 加部 泰明、半田 宏、末松 誠
  • Organizer: 日本ケミカルバイオロジー学会 第6回年会
  • Place of Presentation: 東京工業大学大岡山キャンパス（東京都）
• [Presentation] ヘム/COによるGAPDHを介した細胞防御機構の解明 (2011)
  • Author(s): 加部泰明、内田毅、山本竜也、石森浩一郎、半田宏、末松誠
  • Organizer: 第38回生体分子科学討論会
  • Place of Presentation: 筑波大学（茨城県）
• [Presentation] ガス分子応答性受容体の系統的探索機能解明 (2011)
  • Author(s): 加部泰明、内田毅、山本竜也、堀内正、石森浩一郎、半田宏、末松誠
  • Organizer: 第64回日本酸化ストレス学会
  • Place of Presentation: 北海道ルスツリゾートホテル（北海道）
• [Presentation] Carbon Monoxide Protects Against the GAPDH-mediated Cell Death (2011)
  • Author(s): 加部泰明、山本竜也、半田宏、末松誠
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Book] 実験医学別冊「医学生物学における最新プロトコールと実験例」 (2013)
  • Author(s): 加部泰明, 末松誠, 半田宏
  • Publisher: 羊土社
• [Book] 実験医学別冊「医学生物学における最新プロトコールと実験例」 (2013)
  • Author(s): 加部泰明、末松誠、半田宏
  • Publisher: 羊土社
• [Book] 実験医学別冊、質量分析実験ガイド (2013)
  • Author(s): 加部泰明、末松誠、半田宏
  • Publisher: リガンド結合タンパク質を見つける
• [Book] 臨床麻酔「ガス分子による代謝システム制御機構の系統的探索と応用」 (2012)
  • Author(s): 末松誠, 梶村真弓, 加部泰明.
  • Publisher: 真興交易医書
• [Book] 実験医学「がんと代謝」 (2012)
  • Author(s): 末松誠, 久保亜紀子, 大村光代, 菱木貴子, 梶村真弓, 加部泰明, 杉浦悠基
  • Publisher: 羊土社
• [Book] 実験医学増刊「in vivo実験医学によるヒト疾患解明の最前線」 (2011)
  • Author(s): 末松誠, 梶村真弓, 加部泰明, 山本雄広
  • Publisher: 羊土社
• [Patent(Industrial Property Rights)] 一酸化炭素(CO)による脂肪酸、 コレステロールの取り込み阻害 (2011)
  • Inventor(s): 加部泰明, 末松誠
  • Industrial Property Rights Holder: 加部泰明, 末松誠
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2011-263015
  • Filing Date: 2011-11-17
• [Patent(Industrial Property Rights)] 一酸化炭素（CO）による脂肪酸、コレステロールの取り込み阻害 (2011)
  • Inventor(s): 加部泰明、末松誠
  • Industrial Property Rights Holder: 加部泰明、末松誠
  • Filing Date: 2011