University of Cambridge > > Plant Sciences Departmental Seminars > Salicylic acid and its binding proteins at the crossroads of plant and human health

Salicylic acid and its binding proteins at the crossroads of plant and human health

Add to your list(s) Download to your calendar using vCal

If you have a question about this talk, please contact sb771.

Since our discovery in 1990 that SA regulates plant immunity, we have attempted to determine its mechanisms of action in plant immunity and other biological processes using genetic, molecular, and biochemical approaches. Over two dozen plant SA-binding proteins (SABPs) have been identified primarily through biochemical methods, including three high-throughput screens (Manohar et al., 2015; also see SA binding alters the biochemical and/or biological activities of these proteins, generally by inhibit them. We have extended this work to humans, since the most widely used medicine aspirin (acetyl SA) is rapidly converted to SA after ingestion and SA has most of the same pharmacological activities of aspirin. Two novel targets of SA/aspirin have been identified across the animal and plant kingdoms. Together the two human SAB Ps are associated with most of the major human diseases, including heart attack, stroke, sepsis, rheumatoid arthritis, inflammation-associated cancers, hepatitis, and neurodegenerative diseases. One of the identified human SAB Ps is High Mobility Group Box1 (HMGB1). In addition to its nuclear role in condensing DNA and regulating gene expression, extracellular HMGB1 is a damage-associated molecular pattern (DAMP), which activates immune and inflammatory responses. SA suppresses both the chemo-attractant activity of HMGB1 and the increased expression of pro-inflammatory cytokine and COX -2 genes induced by HMGB1 (Choi et al., 2015a). A synthetic SA derivative acetyl 3-aminoethyl SA and natural derivative from the Chinese medicinal herb Glycyrrhiza foetida (licorice) amorfrutin B1 have been identified, which are much more potent inhibitors than SA of the pro-inflammatory activities of HMGB1 . Interestingly, our parallel study of the plant ortholog AtHMGB3 revealed that it also functions as a DAMP to activate plant immunity. Moreover, it binds SA, which inhibits its immune-inducing activity (Choi et al., 2016). The second novel target in humans is Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH). In addition to its central role in glycolysis, human GAPDH participates in several pathological processes including neuronal cell death associated with Alzheimer’s, Parkinson’s, and Huntington’s diseases. We discovered that SA, like the anti-Parkinson’s drug deprenyl, suppresses nuclear translocation of GAPDH , an early step in cell death, as well as cell death induced by the DNA alkylating agent N-methyl-N-nitroso-N1-nitroguanidine (Choi et al., 2015b). Acetyl 3-aminoethyl SA and amorfrutin B1 not only more tightly bind to GAPDH , but also more effectively suppress nuclear translocation of GAPDH and cell death than SA. In addition to GAPDH ’s role in neuronal cell death, some animal and plant viruses, such as human Hepatitis A, B, C Viruses and Tomato Bushy Stunt Virus (TBSV), usurp this host protein for their replication. We discovered that SA binding to GAPDH inhibits its interaction with the TBSV minus RNA strand, thereby suppressing viral replication. This finding reveals a novel mechanism of SA action in defense against viral pathogens (Tian et al., 2015).

In summary, these studies demonstrate that SA can modulate both plant and human health via shared SAB Ps. Furthermore, the identification of human HMGB1 and GAPDH as pharmacological targets of SA/aspirin provides new insights into the mechanisms of action of one of the world’s longest and most used natural and synthetic drug. It may also provide an explanation for the protective effects of low-dose aspirin usage. Moreover, the identification of natural and synthetic SA derivatives with greater potency for inhibition of HMGB1 and GAPDH provides proof-of-concept that new SA-based compounds with high efficacy are attainable ( Klessig et al., 2016).

This talk is part of the Plant Sciences Departmental Seminars series.

Tell a friend about this talk:

This talk is included in these lists:

Note that ex-directory lists are not shown.


© 2006-2017, University of Cambridge. Contact Us | Help and Documentation | Privacy and Publicity