Global cellular responses to β-methyl-amino-l-alanine (BMAA) by olfactory ensheathing glial cells (OEC)

• Published in: Toxicon (Oxford) Vol. 99; pp. 136 - 145
• Main Authors: Chiu, Alexander S., Braidy, Nady, Marçal, Helder, Welch, Jeffrey H., Gehringer, Michelle M., Guillemin, Gilles J., Neilan, Brett A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2015
• Subjects: Agglomeration; Amino Acids, Diamino - toxicity; Animals; Apoptosis - drug effects; Bacterial Toxins - toxicity; Biotechnology; Cell Line; Cells, Cultured; Channels; Excitatory Amino Acid Agonists - toxicity; G2 Phase - drug effects; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Genes; Genomics; Glial biology; Kinetics; Nerve Tissue Proteins - agonists; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurodegenerative diseases; Neuroglia - cytology; Neuroglia - drug effects; Neuroglia - metabolism; Neurotoxins - toxicity; Olfactory Bulb - cytology; Proteins; Proteomics; Rats; Rats, Wistar; Receptors; β-Methyl-amino-l-alanine; Glial biology; β-Methyl-amino-l-alanine; Neurodegenerative diseases; Genomics; Proteomics
• DOI: 10.1016/j.toxicon.2015.03.009
• ISSN: 0041-0101

This study utilised a proteomics approach to identify any differential protein expression in a glial cell line, rat olfactory ensheathing cells (OECs), treated with the cyanotoxin β-methylamino-l-alanine (BMAA). Five proteins of interest were identified, namely Rho GDP-dissociation inhibitor 1 (RhoGDP1), Nck-associated protein 1 (NCKAP1), voltage-dependent anion-selective channel protein 1 (VDAC1), 3-hydroxyacyl-CoA dehydrogenase type-2 (3hCoAdh2), and ubiquilin-4 (UBQLN4). Four of these candidates, nuclear receptor subfamily 4 group A member 1 (Nur77), cyclophilin A (CyPA), RhoGDP1 and VDAC1, have been reported to be involved in cell growth. A microarray identified UBQLN4, palladin and CyPA, which have been implicated to have roles in excitotoxicity. Moreover, the NCKAP1, UBQLN4, CyPA and 3hCoAdh2 genes have been associated with abnormal protein aggregation. Differential expression of genes involved in mitochondrial activity, Nur77, 3hCoAdh2, VDAC1 and UBQLN4, were also identified. Confirmatory reverse transcription quantitative PCR (RT-qPCR) analysis of transcripts generated from the genes of interest corroborated the differential expression trends identified in the global protein analysis. BMAA induced cell cycle arrest in the G2/M phase of OEC and apoptosis after 48 h at concentrations of 250 μM and 500 μM. Collectively, this work advances our understanding of the mechanism of BMAA-mediated glial-toxicity in vitro. •BMAA induces differential protein expression in rat OECs.•BMAA modulates cell growth, excitotoxicity, and mitochondrial function.•BMAA induced cell cycle arrest in the G2/M phase of OECs and apoptosis.