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Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives
The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA’s multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659538/ https://www.ncbi.nlm.nih.gov/pubmed/26606248 http://dx.doi.org/10.1371/journal.pone.0143447 |
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author | Choi, Hyong Woo Tian, Miaoying Manohar, Murli Harraz, Maged M. Park, Sang-Wook Schroeder, Frank C. Snyder, Solomon H. Klessig, Daniel F. |
author_facet | Choi, Hyong Woo Tian, Miaoying Manohar, Murli Harraz, Maged M. Park, Sang-Wook Schroeder, Frank C. Snyder, Solomon H. Klessig, Daniel F. |
author_sort | Choi, Hyong Woo |
collection | PubMed |
description | The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA’s multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson’s drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N’-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death. |
format | Online Article Text |
id | pubmed-4659538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46595382015-12-02 Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives Choi, Hyong Woo Tian, Miaoying Manohar, Murli Harraz, Maged M. Park, Sang-Wook Schroeder, Frank C. Snyder, Solomon H. Klessig, Daniel F. PLoS One Research Article The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA’s multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson’s drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N’-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death. Public Library of Science 2015-11-25 /pmc/articles/PMC4659538/ /pubmed/26606248 http://dx.doi.org/10.1371/journal.pone.0143447 Text en © 2015 Choi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Choi, Hyong Woo Tian, Miaoying Manohar, Murli Harraz, Maged M. Park, Sang-Wook Schroeder, Frank C. Snyder, Solomon H. Klessig, Daniel F. Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives |
title | Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives |
title_full | Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives |
title_fullStr | Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives |
title_full_unstemmed | Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives |
title_short | Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives |
title_sort | human gapdh is a target of aspirin’s primary metabolite salicylic acid and its derivatives |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659538/ https://www.ncbi.nlm.nih.gov/pubmed/26606248 http://dx.doi.org/10.1371/journal.pone.0143447 |
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