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Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway

Author

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  • Nobuaki Ishihama

    (Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science)

  • Seung-won Choi

    (Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science)

  • Yoshiteru Noutoshi

    (Okayama University)

  • Ivana Saska

    (Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science)

  • Shuta Asai

    (Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science)

  • Kaori Takizawa

    (Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science)

  • Sheng Yang He

    (Michigan State University
    Michigan State University)

  • Hiroyuki Osada

    (Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science)

  • Ken Shirasu

    (Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science
    The University of Tokyo)

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid (SA), target mammalian cyclooxygenases. In plants, SA is a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identify that the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent plant immune response. TNX treatment decreases NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. A cysteine labeling assay reveals that cysteine residues in NPR1 can be oxidized in vitro, leading to disulfide-bridged oligomerization of NPR1, but not in vivo regardless of SA or TNX treatment. Therefore, this study indicates that oxicam inhibits NPR1-mediated SA signaling without affecting the redox status of NPR1.

Suggested Citation

  • Nobuaki Ishihama & Seung-won Choi & Yoshiteru Noutoshi & Ivana Saska & Shuta Asai & Kaori Takizawa & Sheng Yang He & Hiroyuki Osada & Ken Shirasu, 2021. "Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27489-w
    DOI: 10.1038/s41467-021-27489-w
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