Shared and Related Molecular Targets and Actions of Salicylic Acid in Plants and Humans

Abstract

Salicylic acid (SA) is a phenolic compound produced by all plants that has an important role in diverse processes of plant growth and stress responses. SA is also the principal metabolite of aspirin and is responsible for many of the anti-inflammatory, cardioprotective and antitumor activities of aspirin. As a result, the number of identified SA targets in both plants and humans is large and continues to increase. These SA targets include catalases/peroxidases, metabolic enzymes, protein kinases and phosphatases, nucleosomal and ribosomal proteins and regulatory and signaling proteins, which mediate the diverse actions of SA in plants and humans. While some of these SA targets and actions are unique to plants or humans, many others are conserved or share striking similarities in the two types of organisms, which underlie a host of common biological processes that are regulated or impacted by SA. In this review, we compare shared and related SA targets and activities to highlight the common nature of actions by SA as a hormone in plants versus a therapeutic agent in humans. The cross examination of SA targets and activities can help identify new actions of SA and better explain their underlying mechanisms in plants and humans.

Keywords: anti-inflammatory; aspirin; molecular targets; peroxidases; protein phosphorylation; receptors; salicylic acid; systemic acquired resistance.

Figure 1

Roles of NPR receptors in SA-regulated defense responses and SA crosstalk with GA and BR in Arabidopsis. (A) SA binding activates NPR1, which acts as transcription coactivator of TGA transcription factors for SA-mediated gene expression. NPR3 and 4 are transcription repressors but SA can inhibit their repressor activity to release the repression of SA-mediated defense genes. (B) SA receptor NPR1 interacts with the GA receptor GID1 to promote its degradation, thereby enhancing the stability of GA repressor DELLA to inhibit GA signaling and plant growth. (C) SA activates BIN2 kinase, a negative regulator of BR signaling. Activated BIN2 kinase phosphorylates TGA3 transcription factor and enhances its DNA-binding activity but phosphorylates TGA1/4 transcription factors to inhibit their interaction with NPR1 and decreases their stability.

Figure 2

Inhibition of the NF-κB pathway by SA. SA can bind to and inhibit IKK, thereby preventing phosphorylation and degradation of IκB required for activation of NF-κB. Ribosomal protein RPS3 can translocate to the nucleus to activate NF-κB. SA also directly binds to RPS3 to prevent its translocation to the nucleus. The NF-κB pathway can also be inhibited or activated through the p38, ERK and JNK MAPK pathways, which are subjected to inhibition or activation by SA.

Figure 3

Regulation of protein phosphorylation networks by SA in plants. (A) SA-induced MAPK signaling cascade for regulation of defense responses. (B) SA inhibition of root growth through inhibition of PP2A, endocytic recycling and polar distribution of auxin. (C) SA antagonism of ABA signaling through inhibition of PP2C degradation and ABA-stimulated interaction of PP2C and ABA receptors.

Figure 4

Antitumor activity of SA through activation of AMPK. AMPK is activated through phosphorylation of its α and β subunits by LKB1 and CAMKKβ or through allosteric effects on its γ subunit by AMP/ADP. SA can directly bind to and activate AMPK. Activated AMPK phosphorylates and inactivates ACC. Inactivated ACC suppresses fatty acid synthesis and tumor cell growth.

Figure 5

Inhibition of nonmetabolic activities of GAPDH by SA. GAPDHs from both plants and humans participate in a number of nonmetabolic processes including viral replication, cell death, ROS accumulation, disease resistance and autophagy. SA directly binds to GAPDHs and affects the nonmetabolic activities of GAPDH.