TY - JOUR
T1 - Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway
AU - Ishihama, Nobuaki
AU - Choi, Seung won
AU - Noutoshi, Yoshiteru
AU - Saska, Ivana
AU - Asai, Shuta
AU - Takizawa, Kaori
AU - He, Sheng Yang
AU - Osada, Hiroyuki
AU - Shirasu, Ken
N1 - Funding Information:
We thank Dr. Xinnian Dong, Dr. Xin Li, Dr. Mary Wildermuth, Dr. Bethany Huot, and Dr. Yoshihiro Narusaka for sharing materials. We also thank all the members of Ken Shirasu laboratory for fruitful discussions; Dr. Yasuhiro Kadota and Dr. Anuphon Laohavisit for critically reading the manuscripts; and Mrs. Satoko Morino for lab help. This work was supported in part by Grant-in-Aid for Scientific Research (KAKENHI) (15H05959, 17H06172, 20H05909, 19039034, and 24228008 to K.S., 15K18651, 17K07679, and 20H02995 to S.A.).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-021-27489-w
DO - 10.1038/s41467-021-27489-w
M3 - Article
C2 - 34911942
AN - SCOPUS:85121368834
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7303
ER -