活性酸素による多階層シグナル伝達機構とレドックス恒常性制御  [in Japanese] Reactive Oxygen Species Signaling and Redox Homeostasis Regulated by 8-Nitro-cGMP  [in Japanese]

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Author(s)

    • 赤池 孝章 Akaike Takaaki
    • 熊本大学大学院生命科学研究部微生物学分野 Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University

Abstract

  An emerging aspect of redox signaling is the signaling pathway mediated by electrophilic byproducts, such as nitrated cyclic nucleotide (8-nitro-cGMP), generated <i>via</i> reactions of reactive oxygen species (ROS), NO, and their secondary products. We recently clarified that enzymatically-generated hydrosulfide derivatives regulate the metabolism and signaling of 8-nitro-cGMP. Although hydrogen sulfide was proposed to be a gaseous signaling mediator, its exact nature and physiological functions remain obscure. We thus found that particular hydropersulfide derivatives rather than hydrogen sulfide greatly ameliorated chronic heart failure after myocardial infarction <i>in vivo</i> in mice. This potent cardioprotective effect resulted from strong suppression of H-Ras signaling activated by electrophilic stimulation with 8-nitro-cGMP functioning as a second messenger for the redox signaling induced by NO and ROS. A significant amount of 8-nitro-cGMP was formed in the heart tissue after myocardial infarction, and hydrogen sulfide exogenously administered completely nullified this formation. We have reportedly shown that hydropersulfide effectively thiolated electrophiles in cells, which is best represented by 8-nitro-cGMP. Our current study indicates that electrophile thiolation may be a unique mechanism regulating ROS signaling and redox homeostasis, which may thus promote further development of prophylactic and therapeutic options for oxidative stress-related diseases.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 134(4), 515-519, 2014

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130003391199
  • NII NACSIS-CAT ID (NCID)
    AN00284903
  • Text Lang
    JPN
  • ISSN
    0031-6903
  • NDL Article ID
    025431250
  • NDL Call No.
    Z19-411
  • Data Source
    NDL  J-STAGE 
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