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

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.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE154593 | GEO | 2021/11/09

REPOSITORIES: GEO

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Project description:Zhou2015 - Circadian clock with immune regulator NPR1 Arabidopsis clock model modified from P2012 (Pokhilko et al., 2013 - BIOMD0000000445) model to include the master immune regulator NPR1 coupling to LHY, TOC1 and PRR7. Triggers: The Global Quantities contain triggers that allow one to change coupling settings, Salicyclic acid (SA) treatment and npr1 mutants. LHY_on: true->NPR1 couples to LHY PRR7_on: true->NPR1 couples to PRR7 WT: true->WT plants, false->npr1 mutant plants SA: true->SA treated plants, false->no treatment This model has L=1, i.e. operates only under constant light conditions and is not aiming to make preditions under diurnal conditions. Due to period overshoot only time points after 28h are relevant. This model is described in the article: Redox rhythm reinforces the circadian clock to gate immune response. Zhou M, Wang W, Karapetyan S, Mwimba M, Marqués J, Buchler NE, Dong X. Nature 2015 Jun; Abstract: Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism. This model is hosted on BioModels Database and identified by: BIOMD0000000577. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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

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