Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway
© 2021. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Nature communications - 12(2021), 1 vom: 15. Dez., Seite 7303 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ishihama, Nobuaki [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.01.2022 Date Revised 08.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-021-27489-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM334481783 |
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| 100 | 1 | |a Ishihama, Nobuaki |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway |
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| 520 | |a © 2021. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Anti-Inflammatory Agents, Non-Steroidal |2 NLM | |
| 650 | 7 | |a Arabidopsis Proteins |2 NLM | |
| 650 | 7 | |a NPR1 protein, Arabidopsis |2 NLM | |
| 650 | 7 | |a NPR3 protein, Arabidopsis |2 NLM | |
| 650 | 7 | |a Piroxicam |2 NLM | |
| 650 | 7 | |a 13T4O6VMAM |2 NLM | |
| 650 | 7 | |a Salicylic Acid |2 NLM | |
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| 700 | 1 | |a Choi, Seung-Won |e verfasserin |4 aut | |
| 700 | 1 | |a Noutoshi, Yoshiteru |e verfasserin |4 aut | |
| 700 | 1 | |a Saska, Ivana |e verfasserin |4 aut | |
| 700 | 1 | |a Asai, Shuta |e verfasserin |4 aut | |
| 700 | 1 | |a Takizawa, Kaori |e verfasserin |4 aut | |
| 700 | 1 | |a He, Sheng Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Osada, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Shirasu, Ken |e verfasserin |4 aut | |
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