UPA Perpustakaan Universitas Jember

Assessing the Combined Toxicity of BMAA and Its Isomers 2,4-DAB and AEG In Vitro Using Human Neuroblastoma Cells

Brendan J. Main 1 - Personal Name
Kenneth J. Rodgers 1 - Personal Name

The non-protein amino acid (NPAA) ß-
methylamino- L -alanine (BMAA) is produced by a diverse
range of cyanobacteria, diatoms and dinoflagellates, and is
present in both aquatic and terrestrial ecosystems globally.
Exposure to BMAA has been implicated in the development
of neurodegenerative diseases including amyotrophic lateral
sclerosis (ALS), Alzheimer’s disease (AD) and Parkinson’s
disease (PD). BMAA is often found in nature along with its
structural isomers 2,4-diaminobutyric acid (2,4-DAB) and
aminoethylglycine (AEG); however, the toxicity of these
NPAAs in combination has not been examined. We have pre-
viously demonstrated that BMAA induces endoplasmic retic-
ulum (ER) stress and increases caspase and cathepsin activity
in human neuroblastoma cells (SH-SY5Y), effects consistent
with proteotoxic stress due to disturbances in protein synthe-
sis, folding or turnover. The current study investigates whether
2,4-DAB and AEG share a similar mechanism of toxicity to
BMAA, and if simultaneous exposure of cells to BMAA and
its isomers results in increased toxicity in vitro. We show that a
48-h treatment with both 500 μM BMAA and 2,4-DAB de-
creases cell viability in vitro whereas AEG was not cytotoxic
under the same conditions. Treatment of SH-SY5Y cells with
2,4-DAB did not increase expression of ER stress markers.
Combined treatment of cells with BMAA and 2,4-DAB re-
sulted in increased caspase activity and increased apoptosis
above that of BMAA or 2,4-DAB on their own. These results
suggest that 2,4-DAB does not share the same mechanism of

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BMAA
ALS
MND
2,4-DAB
Non-protein amino acids
Unfolded protein response

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Assessing the Combined Toxicity of BMAA and Its Isomers 2,4-DAB and AEG In Vitro Using Human Neuroblastoma Cells

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NPP. 3509212D1000001

Assessing the Combined Toxicity of BMAA and Its Isomers 2,4-DAB and AEG In Vitro Using Human Neuroblastoma Cells

Brendan J. Main 1 - Personal NameKenneth J. Rodgers 1 - Personal Name

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Brendan J. Main 1 - Personal Name
Kenneth J. Rodgers 1 - Personal Name