title: Global cellular responses to β-methyl-amino-L-alanine (BMAA) by olfactory ensheathing glial cells (OEC).
abstract: 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.
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
authors: Alexander S
authors: AS
authors: Chiu
authors: Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, The University of New South Wales, Sydney, Australia.
authors: Nady
authors: N
authors: Braidy
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
authors: Helder
authors: H
authors: Marçal
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
authors: Jeffrey H
authors: JH
authors: Welch
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
authors: Michelle M
authors: MM
authors: Gehringer
authors: Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, Australia.
authors: Gilles J
authors: GJ
authors: Guillemin
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia. Electronic address: b.neilan@unsw.edu.au.
authors: Brett A
authors: BA
authors: Neilan
mesh_terms: D000599:Amino Acids, Diamino / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D016195:G2 Phase / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D009830:Olfactory Bulb / Q000166:cytology; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000599:Amino Acids, Diamino; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine
keywords: Genomics; Glial biology; Neurodegenerative diseases; Proteomics; β-Methyl-amino-l-alanine