TMT-based quantitative proteomic assessment of Vicia sativa induced neurotoxicity by β-cyano-L-alanine and γ-glutamyl-β-cyano-L-alanine in SH-SY5Y cells.
TMT-based quantitative proteomic assessment of Vicia sativa induced neurotoxicity by β-cyano-L-alanine and γ-glutamyl-β-cyano-L-alanine in SH-SY5Y cells.
Riley, S.; Vy Nguyen, V.; Bhattacharjeec, R.; Ng, P. Q.; Ritchie, T. C.; Fisk, I.; Gecz, J.; Kumar, R.; Searle, I. R.
Abstract{beta}-Cyano-L-alanine (BCA) and {gamma}-glutamyl-{beta}-cyano-L-alanine (GBCA) are the primary antinutritional compounds in Vicia sativa, a high--protein, drought-tolerant legume. While neurotoxicity in monogastric animals has been observed, its molecular basis remains largely unknown. In this study, we optimised an in vitro assay using retinoic acid-differentiated SH--SY5Y human neuroblastoma cells to assess BCA and GBCA toxicity and applied TMT-based quantitative proteomics to identify dysregulated proteins. BCA treatment affected proteins involved in DNA damage, translation, and oxidative stress, many of which are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimers disease, as well as various cancers. In contrast, GBCA disrupted proteins linked to mitosis, cell cycle regulation, and apoptosis pathways. Interestingly, the absence of overlapping dysregulated proteins between BCA- and GBCA-treated cells suggests they induce neurotoxicity via distinct mechanisms. These findings offer new insights into the molecular toxicity of V. sativa toxins and their implications for animal feed safety.