Regulation of cystine/glutamate transporter by food-derived factors and its physiological functions

• Project/Area Number: 21380074
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: Yamagata University
• Principal Investigator: SATO Hideyo 山形大学, 農学部, 教授 (60235380)
• Co-Investigator(Kenkyū-buntansha): IGARASHI Kiharu 山形大学, 農学部, 教授 (00111336)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
• Keywords: 食品 / グルタチオン / シスチン / トランスポーター / ネギ科植物 / 酸化ストレス / フラボノイド / レドックス / グルタミン酸

Research Abstract

In the present study, we have investigated the regulatory mechanism of cystine/glutamate transporter (xCT) by food-derived factors and the physiological functions. xCT is constitutively expressed in immune tissues including mesenteric lymph node and Payer's patch. Induction of xCT in macrophages has been demonstrated to be important for expressing the function of the cells. The extract derived from some species of Allium increased intracellular glutathione. This was due to the induction of xCT. Increased glutathione in islet cells by the extract from Allium plants seems to play a protective role against oxidative stress.

Research Products

• [Journal Article] Mutation of ATF4 mediates resistance of neuronal cell lines against oxidative stress by inducing xCT expression (2012)
  • Author(s): Lewerenz, J., Sato, H., Albrecht, P., Henke, N., Noack, R., Methner, A., Maher, P
  • Journal Title: Cell Death & Differentiation Volume: 19 Pages: 847-858
  • Peer Reviewed
• [Journal Article] The oxidative stress-inducible cystine/glutamate antipoter, System xc- : cystine supplier and beyond (2012)
  • Author(s): Conrad, M., Sato, H.
  • Journal Title: Amino Acids Volume: 42 Issue: 1 Pages: 231-246
  • DOI: 10.1007/s00726-011-0867-5
  • Peer Reviewed
• [Journal Article] The oxidative stress-inducible cystine/glutamate antipoter, System xc-: cystine supplier and beyond (2011)
  • Author(s): Conrad, M., Sato, H
  • Journal Title: Amino Acids Volume: 42 Pages: 231-246
  • Peer Reviewed
• [Journal Article] Dopaminergic neurons of system xc-deficient mice are highly protected against 6-OHDA induced toxicity (2011)
  • Author(s): Massie, A., Schallier, A., Kim, S-W., Fernando, R., Kobayashi, S., Beck, H., De Bundel, D., Vermoesen, K., Bannai, S., Conrad, M., Plesnila, N., Sato, H., Michotte, Y
  • Journal Title: FASEB J Volume: 25 Pages: 1359-1369
  • Peer Reviewed
• [Journal Article] Loss of system xc-does not induce oxidative stress but decrease extracellular glutamate in hippocampus and influences spatial working memory and limbic seizure susceptibility (2011)
  • Author(s): De Bundel, D., Schallier, A., Loyens, E., Fernando, R., Miyashita, H., Van Liefferinge, J., Vermoesen, K., Bannai, S., Sato, H., Michotte, Y., Smolders, I., Massie, A
  • Journal Title: J. Neurosci Volume: 31 Pages: 5792-5803
  • Peer Reviewed
• [Journal Article] Anti-diabetic effects of Actinidia arguta polyphenols on rats and KK-A^y mice (2011)
  • Author(s): Kurakane, S., Yamada, N., Sato, H., Igarashi, K
  • Journal Title: Food Sci. Technol. Res Volume: 17 Pages: 93-102
  • NAID: 10028188956
  • Peer Reviewed
• [Journal Article] Anti-diabetic effects of kaempferol glycoside-rich fraction from unripe-soybean (Edamame, Glycine max. L. Merrill. 'Jindai') leaves on KK-A^y mice (2011)
  • Author(s): Zang, Y., Sato, H., Igarashi, K
  • Journal Title: Biosci. Biotechnol. Biochem Volume: 75 Pages: 1677-1684
  • NAID: 130000940061
  • Peer Reviewed
• [Journal Article] MMDB : Mouse multiple tissue metabolome database (2011)
  • Author(s): Sugimoto, M., Ikeda, S., Niigata, K., Tomita, M., Sato, H., Soga, T
  • Journal Title: Nucleic Acids Res Pages: 1-6
  • Peer Reviewed
• [Journal Article] Anti-Diabetic Effects of a Kaempferol Glycoside-Rich Fraction from Unripe Soybean (Edamame, Glycine max L. Merrill. 'Jindai') Leaves on KK-Ay Mice (2011)
  • Author(s): Zang, Y., et al.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 75 Issue: 9 Pages: 1677-1684
  • DOI: 10.1271/bbb.110168
  • NAID: 130000940061
  • ISSN: 0916-8451, 1347-6947
  • Peer Reviewed
• [Journal Article] MMDB : Mouse multiple tissue metabolome database (2011)
  • Author(s): Sugimoto, M., et al.
  • Journal Title: Nucleic Acids Res Volume: 2011 Issue: D1 Pages: 1-6
  • DOI: 10.1093/nar/gkr1170
  • Peer Reviewed
• [Journal Article] Dopaminergic neurons of system xc deficient mice are highly protected against 6-OHDA induced toxicity. (2011)
  • Author(s): Massie, A., et al.
  • Journal Title: FASEB J. Volume: 25 Pages: 1359-1369
  • Peer Reviewed
• [Journal Article] Loss of system xcdoes not induce oxidative stress but decrease extrace llular glutamate in hippocampus and influences spatial working memory and limbic seizure susceptibility. (2011)
  • Author(s): De Bundel, D., et al.
  • Journal Title: J.Neurosci. Volume: 31 Pages: 5792-5803
  • Peer Reviewed
• [Journal Article] System XC-and thioredoxin reductase 1 cooperatively rescue glutathione deficiency (2010)
  • Author(s): Mandal, P. K., Seiler, A., Perisic, T., Kolle, P., Canak, A. B., Forster, H., Weiss, N., Kremmer, E., Lieberman, M. W., Bannai, S., Kuhlencordt, P., Sato, H., Bornkamm, G. W., Conrad, M
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 22244-22253
  • Peer Reviewed
• [Journal Article] System xc and thioredoxin reductase 1 cooperatively rescue glutathione deficiency. (2010)
  • Author(s): Mandal, P.K., et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 22244-22253
  • Peer Reviewed
• [Journal Article] Transforming Growth Factor-B1 elicits Nrf2-mediated antioxidant responses in aortic smooth muscle cells. (2009)
  • Author(s): Churchman, A.T., et al.
  • Journal Title: J.Cell.Mol.Med. 13 Pages: 2282-2292
  • Peer Reviewed
• [Journal Article] Anti-diabetic effects of pumpkin and its components, trigonelline and nicotinic acid, on Goto-Kakizaki rats. (2009)
  • Author(s): Yoshinari, O., et al.
  • Journal Title: Biosci.Biotechnol.Biochem. 73 Pages: 1033-1041
  • Peer Reviewed
• [Journal Article] Aggravation of ischemia-reperfusion-triggered acute renal failure in xCT-deficient mice. (2009)
  • Author(s): Shibasaki, T., et al.
  • Journal Title: Arch.Biochem.Biophys. 491 Pages: 63-69
  • Peer Reviewed
• [Presentation] Cystine/glutamate antiporter : Light and shadow under physiological and pathophysiological contidions (2012)
  • Author(s): Sato, H.
  • Organizer: UK-Japan Research Symposium
  • Place of Presentation: つくば市(つくばサイエンスインフォメーションセンター)
• [Presentation] Role of cystine/glutamate transporter, System X_c^-, on NO release from macrophages (2011)
  • Author(s): 小林翔、三瓶陽太、筒井拓己、井川奈保、柳大樹、五十嵐喜治、坂内四郎、佐藤英世
  • Organizer: 第34回日本分子生物学会大会
  • Place of Presentation: 横浜市(パシフィコ横浜)
  • Year and Date: 2011-12-15
• [Presentation] Role of cystine/glutamate transporter, System X_e, on NO release from macrophages (2011)
  • Author(s): 小林翔, 他
  • Organizer: 第34回日本分子生物学会大会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-12-15
• [Presentation] 肺胞マクロファージにおけるシスチン・グルタミン酸トランスポーターの発現と機能 (2010)
  • Author(s): 小林翔, 土田雄介, 笠越隆幸, 小倉美雪, 佐藤寛, 五十嵐喜治, 坂内四郎, 佐藤英世
  • Organizer: 第83回日本生化学会・第33回日本分子生物学会合同大会
  • Place of Presentation: 神戸市(神戸国際展示場)
  • Year and Date: 2010-12-07
• [Presentation] 肺胞マクロファージにおけるシスチン・グルタミン酸トランスポーターの発現と機能 (2010)
  • Author(s): 小林翔, 他
  • Organizer: 第83回日本生化学会・第33回日本分子生物学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 培養系マウス卵の初期発生におけるグルタチオンおよびシスチン・グルタミン酸トランスポーターの役割 (2010)
  • Author(s): 高野智枝, 酒出はるな, 佐藤英世, 戸津川清, 木村直子
  • Organizer: 第103回日本繁殖生物学会大会
  • Place of Presentation: 十和田市(北里大学獣医学部)
  • Year and Date: 2010-09-03
• [Presentation] シスチン・グルタミン酸トランスポーター(xCT)遺伝子欠損マウス由来受精卵の体外発生能 (2010)
  • Author(s): 高野智枝, 木村直子, 佐藤英世, 戸津川清
  • Organizer: 第51回日本哺乳動物卵子学会
  • Place of Presentation: 新潟市(朱鷺メッセ)
  • Year and Date: 2010-05-30
• [Presentation] 皮膚炎症反応におけるレドックスバランス制御 (2009)
  • Author(s): 岡田卓巳, 佐藤英世, 渡辺直子
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜市(パシフィコ横浜)
  • Year and Date: 2009-12-11
• [Presentation] 皮層炎症反応におけるレドックスバランス制御 (2009)
  • Author(s): 岡田卓巳, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-12-11
• [Presentation] Physiological relevance of ischemia/reperfusion-induced xCT expression in kidneys : corroborating evidence in xCT-deficient mice (2009)
  • Author(s): 柴崎智弘, 井内良仁, 岡田太, 桑田一歩, 山辺拓也, 坂内四郎, 冨田善彦, 佐藤英世, 藤井順逸
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸市(神戸国際展示場)
  • Year and Date: 2009-10-22
• [Presentation] 哺乳類培養細胞のシスチン・グルタミン酸トランスポーターの発現における多価不飽和脂肪酸の影響 (2009)
  • Author(s): 小林翔, 大林亮介, 菅野裕司, 土田雄介, 柳大樹, 坂野麻里子, 五十嵐喜治, 坂内四郎, 佐藤英世
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸市(神戸国際展示場)
  • Year and Date: 2009-10-22
• [Presentation] 哺乳類培養細胞のシスチン・グルタミン酸トランスポーターの発現における多価不飽和脂肪酸の影響 (2009)
  • Author(s): 小林翔, 他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸市
  • Year and Date: 2009-10-22
• [Presentation] Effect of cystine transporter on cutaneous inflammation (2009)
  • Author(s): Watanabe, N., Okada, T., Sato, H
  • Organizer: The 6^<th> Joint Seminar on Biomedical Sciences
  • Place of Presentation: 東京都大田区(東邦大学医学部)
  • Year and Date: 2009-10-16
• [Presentation] Protective role of System xc- in vivo against oxidative stress. (2009)
  • Author(s): Sato, H.
  • Organizer: 11^<th> International Congress on Amino acids, Peptides. and Proteins
  • Place of Presentation: ウィーン(オーストリア)
  • Year and Date: 2009-08-05
• [Presentation] Protective role of System xc-in vivo against oxidative stress (2009)
  • Author(s): Sato, H
  • Organizer: 11^<th> International Congress on Amino acids, Peptides, and Proteins
  • Place of Presentation: Vienna, Austria
• [Remarks]
  • URL: http://www.tr.yamagata-u.ac.jp/~shide/index.html