Oxicam-type nonsteroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway
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PROVIDER: PRJNA646744 | ENA |
REPOSITORIES: ENA
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Project description: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.
2021-11-09 | GSE154593 | GEO
Project description:Salicylic acid (SA) is a plant defense hormone required for immunity. Arabidopsis NPR1 and NPR3/NPR4 were previously shown to bind SA and proposed as SA receptors. However, unlike NPR1, loss of NPR3/NPR4 does not block SA-induced defense gene expression. Here we report that NPR3/NPR4 function as transcriptional repressors and SA inhibits their activities to promote the expression of key immune regulators. npr4-4D, a newly identified gain-of-function allele that renders NPR4 unable to bind SA, constitutively represses SA-induced immune responses. In contrast, the equivalent mutation in NPR1 abolishes its function in promoting SA-induced defense gene expression. Further analysis revealed that npr4-4D and npr1-1 have additive effect on blocking SA-induced defense gene expression, suggesting that NPR4 and NPR1 function in parallel to regulate SA-induced immune responses. Our study reveals the molecular functions of SA receptors NPR3/NPR4 and uncovers a brand new mechanism of SA perception.
2018-06-08 | GSE110702 | GEO
Project description: Not available
| S-EPMC8674334 | biostudies-literature
Project description:The plant immune hormone salicylic acid (SA) modulates transcriptional reprogramming via controlling the master transcriptional coactivator, NPR1. Here we examined the role of HECT-type ubiquitin ligases, UPL1 and UPL5, in SA/NPR1-dependent transcriptional control. We showed that UPL1 and UPL5 are essential regulators of SA-responsive genes, and regulate SA-induced transcriptional reprogramming in a NPR1-dependent manner. Four-week old Arabidopsis thaliana plants of wild-type Col-0, mutant upl1, mutant upl5, and mutant npr1-1 genotypes were germinated on soil in 100% relative humidity. Plants were continuously grown in an environmental chamber with 16/8 hour day/night light regime (120 mol m-2 s-1 light intensity), 21/18 degrees celcius day/night cycle and 65% relative humidity. 4-week-old plants were sprayed with water or 0.5 mM SA until all leaves were thoroughly covered with fine droplets, samples were collected after 24 hours treatment. In total two independent biological repeats were collected.
2021-10-05 | E-MTAB-10963 | biostudies-arrayexpress
Project description:Salicylic acid (SA) and ethylene (ET) are two important plant hormones that regulate numerous plant growth, development, and stress response processes. Previous studies have suggested functional interplay of SA and ET in defense response, but precisely how these two hormones co-regulate plant growth and development processes remains unclear. The present findings reveal an antagonism between SA and ET in apical hook formation, a process that ensures successful soil emergence of dicotyledonous etiolated seedlings. Exogenous SA inhibited the ET-induced expression of HOOKLESS1 (HLS1) in a manner dependent on ETHYLENE INSENSITIVE3 (EIN3)/EIN3-LIKE1 (EIL1), the core transcription factors in the ET signaling pathway. We found that SA-activated NONEXPRESSER OF PR GENES1 (NPR1) physically interacted with EIN3 and interfered with the direct binding of EIN3 to target gene promoters, including the HLS1 promoter. Transcriptomic analysis further revealed that NPR1 and EIN3/EIL1 coordinately regulated subsets of genes that mediate plant growth and stress responses, suggesting that the interaction between NPR1 and EIN3/EIL1 might be an important mechanism for integrating the SA and ET signaling pathways in multiple physiological processes. Taken together, our findings shed light on the molecular mechanism underlying SA regulation of apical hook formation as well as the antagonism between SA and ET in early seedling establishment and possibly other physiological processes.
2020-08-20 | GSE137212 | GEO
Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs) has been suggested as adjunctive anti-tumor agents in human and veterinary medicine. However, its anti-tumor molecular machinery is still controversial. Therefore, we performed whole transcriptome analysis to discover gene expression influenced by NSAIDs treatment.
2016-03-09 | GSE78988 | GEO
Project description:Activation of plant immunity is associated with dramatic transcriptome reprogramming to prioritise immune responses over normal cellular functions. Changes in gene expression are coordinated by the immune hormone salicylic acid (SA). Here we investigated the involvement of the E4 ubiquitin ligase UBE4/MUSE3 in SA-induced transcriptional reprogramming. We show that loss of UBE4 function results in amplified expression of SA-induced, NPR1-dependent gene expression. Twelve-day old Arabidopsis thaliana seedlings of wild-type Col-0, mutant ube4 (SAIL_713_A12) and mutant npr1-1 genotypes were grown on MS media supplemented with 1X Gamborg vitamins in an environmental chamber with 16/8 hour day/night light regime (120 mol m-2 s-1 light intensity) and 22 degrees Celcius. Seedlings were then transferred to 6-well plates and immersed in 10 ml of 0.5 mM SA or water. After 12 hours seedlings were harvested and for each treatment ~50 seedlings were pooled together into a single biological repeat. In total two independent biological repeats were collected. After harvesting seedlings were briefly dried on tissue and immediately frozen in liquid nitrogen until further analysis.
2019-03-20 | E-MTAB-7369 | biostudies-arrayexpress
Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs) has been suggested as adjunctive anti-tumor agents in human and veterinary medicine. However, its anti-tumor molecular machinery is still controversial. Therefore, we performed whole transcriptome analysis to discover gene expression influenced by NSAIDs treatment. A canine melanoma cell line (Mi/CMM1) was treated by three NSAIDs, piroxicam, carprofen, and robenacoxib, at their half maximal (50%) inhibitory concentrations (116 µM, 779 µM, and 156 µM) for 6 hours. Subsequently, total RNA were extracted and microarray analysis was performed to evaluate change in gene expression caused by NSAIDs treatment. Each condition had three biological replicates.
2016-03-09 | E-GEOD-78988 | biostudies-arrayexpress
Project description:BRCA2A: We used microarrays to identify differentially expressed genes. We focused on those genes that were dramatically salicylic acid-induced (>2-fold) and BRCA2A-dependent in npr1 sni1 double mutants. SSN2: We used microarrays to identify differentially expressed genes. We focused on those genes that were dramatically salicylic acid-induced (P<0.05) and SSN2-dependent in npr1 sni1 double mutants. BRCA2A: 3-week old npr1 sni1 and npr1 sni1 brca2a mutants were treated with salicylic acid for 16 hours. Replicates are derived from three independent biological experiments. SSN2: 3-week old npr1 sni1 ssn2 mutants were treated with salicylic acid for 16 hours. Replicates are derived from two (SA treated) or three (water treated) independent biological experiments.
2010-11-21 | E-GEOD-23617 | biostudies-arrayexpress
Project description:<p><strong>BACKGROUND:</strong> Large-scale, placebo-controlled trials established that nonsteroidal anti-inflammatory drugs confer a cardiovascular hazard: this has been attributed to depression of cardioprotective products of cyclooxygenase (COX)-2, especially prostacyclin. An alternative mechanism by which nonsteroidal anti-inflammatory drugs might constrain cardioprotection is by enhancing the formation of methylarginines in the kidney that would limit the action of nitric oxide throughout the vasculature.</p><p><strong>METHODS:</strong> Targeted and untargeted metabolomics were used to investigate the effect of COX-2 deletion or inhibition in mice and in osteoarthritis patients exposed to nonsteroidal anti-inflammatory drugs on the l-arginine/nitric oxide pathway.</p><p><strong>RESULTS:</strong> Analysis of the plasma and renal metabolome was performed in postnatal tamoxifen-inducible Cox-2 knockout mice, which exhibit normal renal function and blood pressure. This revealed no changes in arginine and methylarginines compared with their wild-type controls. Moreover, the expression of genes in the l-arginine/nitric oxide pathway was not altered in the renal medulla or cortex of tamoxifen inducible Cox-2 knockout mice. Therapeutic concentrations of the selective COX-2 inhibitors, rofecoxib, celecoxib, and parecoxib, none of which altered basal blood pressure or renal function as reflected by plasma creatinine, failed to elevate plasma arginine and methylarginines in mice. Finally, plasma arginine or methylarginines were not altered in osteoarthritis patients with confirmed exposure to nonsteroidal anti-inflammatory drugs that inhibit COX-1 and COX-2. By contrast, plasma asymmetrical dimethylarginine was increased in mice infused with angiotensin II sufficient to elevate blood pressure and impair renal function. Four weeks later, blood pressure, plasma creatinine, and asymmetrical dimethylarginine were restored to normal levels. The increase in asymmetrical dimethylarginine in response to infusion with angiotensin II in celecoxib-treated mice was also related to transient impairment of renal function.</p><p><strong>CONCLUSIONS:</strong> Plasma methylarginines are not altered by COX-2 deletion or inhibition but rather are elevated coincident with renal compromise.</p><p><br></p><p><strong>Murine kidney and plasma UPLC-MS/MS assay</strong> protocols and data are reported in the current study <strong>MTBLS680</strong>.</p><p><strong>Murine and human plasma quantitative L-arginine and methylarginines UPLC-MS/MS assay</strong> protocols and data are reported in <a href="https://www.ebi.ac.uk/metabolights/MTBLS685" target="_blank"><strong>MTBLS685</strong></a>.</p>
2019-08-22 | MTBLS680 | MetaboLights