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Redox Regulation of Signal Transduction Mechanism in the Heart

Research Project

Project/Area Number 13470483
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKyushu University (2002)
The University of Tokyo (2001)

Principal Investigator

KUROSE Hitoshi  Kyushu University Pharmacology and Toxicology Professor, 大学院・薬学研究院, 教授 (10183039)

Co-Investigator(Kenkyū-buntansha) NAGAO Tanku  National Institute of Food Drug and Health Head, 所長(研究職) (30217971)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2002: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2001: ¥8,900,000 (Direct Cost: ¥8,900,000)
Keywordsreactive oxygen species / oxidative stress / cysteine residue / G protein / signaling molecule / intracellular mediator / 酸素毒性 / 細胞保護 / セリン変異体
Research Abstract

Reactive oxygen species (ROS) has been considered as an 'evil player' due to a strong reactivity. We have reported that trimeric G protein (G_i/G_0) is directly activated by one of ROS hydrogen peroxide (H_2O_2) in rat neonatal myocytes. Upon activation of G_i/G_0 by H_2O_2, Gβγis released from trimeric G_i/G_0 and the released Gβγ activates ERK to protect the cells against oxidative damage. We have now identified the amino acids that are modified by H_2O_2, and have found that the H_2O_2-mediated modification of cysteine residues located at 287 and 326 is necessary for activation of G_i. These results indicate that ROS can work as an intracellular mediator in the heart, and suggest that ROS generated by receptor stimulation can activate G_i and G_0. Other than the treatment of cells with H_2O_2, ROS was generated by receptor stimulation. Although angiotensin II stimulation generated ROS and induced MAP kinase activation, angiotensin II stimulation could not activate G_i and G_0. Therefore, we concluded that the amount of ROS is an important factor for activation of G protein. We have also found that the expression of peroxiredoxin II (PrxII) eliminates ROS from cells, and PrxII abolishes c-Jun NH_2-terminal kinase (JNK) activation without affecting ERK and p38 MAPK activation. It is concluded that angiotensin II activates specific signaling pathway leading to JNK activation. It also suggests that ROS can work as an intracellular mediator.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(33 results)

All Other

All Publications (33 results)

  • [Publications] Shiina, T. et al.: "Low affinity of β_1-adrenergic receptor for β-arrestins explains the resistance to agonist-induced internalization"Life Sci.. 68. 2251-2257 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiina, T. et al.: "Clathrin box in G protein-coupled receptor kinase 2"J. Biol. Chem.. 276. 33019-33026 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara, Y. et al.: "LTRPC2 Ca2+-permeable channel activated by changes in redox confers susceptibility to cell death"Mol. Cell. 9. 163-172 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishida, M. et al.: "Activation mechanism of G_i and G_o by reactive oxygen species"J. Biol. Chem.. 277. 9036-9042 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishida, M. et al.: "Gβγ counteracts Gα_q signaling upon α_1-adrenergic receptor stimulation"Biochem. Biophys. Res. Commun.. 291. 995-1000 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Endo, A. et al.: "Sphingosine 1-phosphate induces membrane ruffling and increases motility of human umbilical vein endothelial cells via vascular endothelial growth factor receptor and CrkII"J. Biol. Chem.. 277. 23747-23754 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Isogaya, M. et al.: "Enhanced cAMP response of the naturally occurring mutant of human β_3-adrenoceptor"Jpn. J. Pharmacol.. 88. 314-318 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugimoto, Y. et al.: "β_1-Selective agonist (-)-1-(3,4-dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] differentially interacts with key amino acids responsible for β_1-selective binding in resting and active states"J. Pharmacol. Exp. Ther.. 301. 51-58 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maruyama, Y. et al.: "Gα_<12/13> mediate α_1-adrenergic receptor-induced cardiac hypertrophy"Circ. Res.. 91. 961-969 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arai, K. et al.: "Differential requirement of Gα_<12>, Gα_<13>, Gα_q and Gβγ for endothelin-1-induced JNK and ERK activation"Mol. Pharmacol.. 63. 478-488 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ahmed, M. et al.: "Binding and functional affinity of some newly synthesized phenethylamine and phenoxypropanolamine derivatives for their agonistic activity at recombinant human β_3-adrenoceptor"J. Pharm. Pharmacol.. 55. 95-101 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiia, T., Nagao T. and Kurose H.: "Low affinity of β_i-adrenergic receptor for β-arrestins explains the resistance to agonist-induced internalization"Life Sci.. 68. 2251-2257 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiina T., Arai K, Tanabe S., Yoshida N., Haga T., Nagao T., and Kurose H.: "Clathrin box in G protein-coupled receptor kinase 2"J. Biol. Chem.. 276. 33019-33026 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara Y., Wakamori M., Ishii M., Maeno E., Nishida M., Yoshida T., Yamada H., Shimizu S., Mori E., Kudoh J., Shimizu N., Kurose H., Okada Y., Imoto K., Mori Y.: "LTRPC2 Ca^<2+>-permeable channel activated by changes in redox status confers susceptibility to cell death"Mol. Cell. 9. 163-172 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishida M., Schey K., Takagahara S., Kontani K., Katada T., Urano Y., Nagano T., Nagao T., and Kurose H.: "Activation mechanism of G_i and G_0 by reactive oxygen species."J. Biol. Chem.. 277. 9036-9042 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishida M., Takagahara S., Maruyama Y., Sugimoto Y., Nagao T., and Kurose H.:: "Gβγ counteracts Gα_q signaling upon β_1-adrenergic receptor stimulation"Biochem. Biophys. Res. Commun.. 291. 995-1000 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Endo A., Nagashima K., Kurose H., Mochizuki S., Matsuda M., and Mochizuki N.: "Sphingosine 1-phosphate induces membrane ruffling and increases motility of human umbilical vein endothelial cells via vascular endothelial growth factor receptor and CrkII."J. Biol. Chem.. 277. 23747-23754 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Isogaya M., Nagao T., and Kurose H.: "Enhanced cAMP response of the naturally occurring mutant of human β_3-adrenoceptor"Jpn. J. Pharamcol.. 88. 314-318 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugimoto Y., Fujisawa R., Tanimura R., Lattion, A. L., Cotecchia S., Tujimoto G., Nagao T., and Kurose H.: "β_1-Selective agonist (-)-1-(3,4-dimethoxyphenetylamino)-3-(3, 4-dihydroxy)-2-propanol [(-)-RO363] differentially interacts with key amino acids responsible for β_1-selective binding in resting and active states"J. Pharmacol. Exp. Ther.. 301. 51-58 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maruyama Y., Nishida M., Sugimoto Y., Tanabe S., Turner J. H., Kozasa T., Wada T., Nagao T., and Kurose H.: "Gα_<12/13> Mediate α_1-Adrenergic Receptor-induced Cardiac Hypertrophy"Circ. Res.. 91. 961-969 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arai K., Maruyama Y., Nishida Tanabe S., Takagahara S., Turner J. H., Kozasa T., Mori Y., Nagao T., and Kurose H.: "Differential requirement of Gα_<12>, Gα_<13>, Gα_q and Gβγ for endothelin-1-induced JNK and ERK activation"Mol. Pharmacol.. 63. 478-488 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ahmed M., Hanaoka Y., Nagatomo T., Kiso T., Kaita T., Kurose H., and Nagao T.: "Binding and functional affinity of some newly synthesized phenethylamine and phenoxypropanolamine derivatives for their agonistic activity at recombinant human β_3-adrenoceptor"J. Pharm. Pharmacol.. 55. 95-101 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shina, T. et al.: "Low affinity of β_1-adrenergic receptor for β-arrestins explains the resistance to agonist-induced internalization"Life Sci.. 68. 2251-2257 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shiina, T. et al.: "Clathrin box in G protein-coupled receptor kinase2"J. Biol. Chem.. 276. 33019-33026 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishida, M. et al.: "Activation mechanism of G_i and G_O by reactive oxygen species"J. Biol. Chem.. 277. 9036-9042 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishida, M. et al.: "Gβγ counteracts Gα_q signaling upon α_1-adrenergic receptor stimulation"Biochem. Biophys. Res. Commun.. 291. 995-1000 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Endo, A. et al.: "Sphingosine 1-phosphate induces membrane ruffling and increases motility of human umbilical vein endothelial cells via vascular endothelial growth factor receptor and CrkII"J. Biol. Chem.. 277. 23747-23754 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Isogaya.M.et al.: "Enhanced cAMP response of the naturally occurring mutant of human β_3-adrenoceptor"Jpn. J. Pharamacol.. 88. 314-318 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shima, T.: "Low affinity of β_1-adrenergic receptor for β-arrestins explains the resistance to agonist-indused internalization"Life Sci.. 68. 2251-2257 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 黒瀬 等: "活性酸素種とGタンパク質"生化学. 73. 553-556 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 西田 基宏: "虚血障害とGタンパク質"ファルマシア. 37. 285-289 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shiina, T.: "Clathrin box in G protein-coupled receptor kinase 2"J.Biol.Chem.. 276. 33019-33026 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishida, M.: "Activation mechanism of G_i and G_o by reactive oxygen species"J.Biol.Chem.. 277(in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-03-31   Modified: 2016-04-21  

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