Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells

Abstract

Objectives Glyphosate ( N -phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome. Results Comparative statistical analysis of global proteome changes between glyphosate treated and non-treated samples did not show significant differences. Crucially, filtering of data to focus analysis on peptides potentially bearing glycine for glyphosate replacement revealed that the TMT reporter intensity pattern of all candidates showed conclusively that they are all false discoveries, with none displaying the expected TMT pattern for such a substitution. Thus, the assertion that glyphosate substitutes for glycine in protein polypeptide chains is incorrect. Electronic supplementary material The online version of this article (10.1186/s13104-019-4534-3) contains supplementary material, which is available to authorized users.

Glyphosate Interaction with eEF1α1 Indicates Altered Protein Synthesis: Evidence for Reduced Spermatogenesis and Cytostatic Effect

“… 14 Further, it has been suggested that glyphosate is a substitute for glycine in protein polypeptide chains, 15 but another study has negated this assumption. 16 Molecular modeling has shown that glyphosate binding to glycyl-tRNA synthetase is unlikely, 16 but the same study did not indicate any significant changes in human breast cancer cells via proteomic analysis, which was similar to another previous study by Mesnage et al, 17 who did not observe changes in MDA-MB-231 cell growth characteristics after treatment with 100 mg/L glyphosate. 16 However, Mesnage et al 17 observed that ≥10 mg/L glyphosate treatment promotes proliferation in MCF-7 cells because these cells are estrogen receptor (ER)-positive.…”

“… 16 Molecular modeling has shown that glyphosate binding to glycyl-tRNA synthetase is unlikely, 16 but the same study did not indicate any significant changes in human breast cancer cells via proteomic analysis, which was similar to another previous study by Mesnage et al, 17 who did not observe changes in MDA-MB-231 cell growth characteristics after treatment with 100 mg/L glyphosate. 16 However, Mesnage et al 17 observed that ≥10 mg/L glyphosate treatment promotes proliferation in MCF-7 cells because these cells are estrogen receptor (ER)-positive. Importantly, the MDA-MB-231 cell line used by Antoniou et al 16 is ER-negative (triple negative) and insensitive to antiestrogen treatments.…”

“… 16 However, Mesnage et al 17 observed that ≥10 mg/L glyphosate treatment promotes proliferation in MCF-7 cells because these cells are estrogen receptor (ER)-positive. Importantly, the MDA-MB-231 cell line used by Antoniou et al 16 is ER-negative (triple negative) and insensitive to antiestrogen treatments. 18 , 19 Furthermore, a previous study hypothesized that glyphosate and AMPA, as glycine analogues, inhibit serine hydroxymethyltransferase (SHMT), which catalyzes serine to glycine and vice versa .…”

Effect of zinc supplementation on chronic hepatorenal toxicity following oral exposure to glyphosate-based herbicide (Bushfire®) in rats

“…However, chronic glyphosate exposure did not significantly affect these values, indicating that the compensatory synthetic capacity of the liver was sustained despite any toxicity. 37 It has been reported that the global proteome of rapidly-dividing cells was not impacted by exposure to glyphosate, implying that glyphosate might not impair protein synthesis and protein metabolism.…”

Pleiotropic Outcomes of Glyphosate Exposure: From Organ Damage to Effects on Inflammation, Cancer, Reproduction and Development

“…The replacement of glyphosate with preserved glycine residues might explain, in part, the reason for the correlation between glyphosate exposure and the onset of various diseases [32]. In fact, recent findings obtained in MDA-MB-231 breast cancer cells did not show any difference between global proteome changes in glyphosate treated and untreated cells; only ADP/ATP translocase and serine/argininerich-splicing factor 6 exhibited statistically significant modifications in glyphosate treated cells [33], suggesting that the pesticide can target specific proteins. Indeed, glyphosate exposure seems to be involved in various diseases of modern era, such as obesity, diabetes, liver and kidney dysfunction, autism, dementia, Parkinson's and Alzheimer's disease, leukemia, various forms of cancer and inflammatory diseases.…”