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L-BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations

L-BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations

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Prüfsumme: MD5:469b764d9c62f241173afbaf9f335484

OKLE, Oliver, Kerstin STEMMER, Ulrich DESCHL, Daniel R. DIETRICH, 2013. L-BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations. In: Toxicological Sciences. 131(1), pp. 217-224. ISSN 1096-6080. eISSN 1096-0929. Available under: doi: 10.1093/toxsci/kfs291

@article{Okle2013-01LBMAA-28478, title={L-BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations}, year={2013}, doi={10.1093/toxsci/kfs291}, number={1}, volume={131}, issn={1096-6080}, journal={Toxicological Sciences}, pages={217--224}, author={Okle, Oliver and Stemmer, Kerstin and Deschl, Ulrich and Dietrich, Daniel R.} }

Dietrich, Daniel R. Deschl, Ulrich L-BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations 2014-07-31T14:48:44Z Dietrich, Daniel R. The cyanobacterial β-N-methylamino-l-alanine (l-BMAA) is described as a low-potency excitotoxin, possibly a factor in the increased incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) in Guam. The latter association is intensively disputed, as l-BMAA concentrations required for toxic effects exceed those assumed to occur via food. The question thus was raised whether l-BMAA leads to neurodegeneration at nonexcitotoxic conditions. Using human SH-SY5Y neuroblastoma cells, l-BMAA-transport, incorporation into proteins, and subsequent impairment of cellular protein homeostasis were investigated. Binding of l-BMAA to intracellular proteins, but no clear protein incorporation was detected in response to <sup>14</sup>C-l-BMAA exposures. Nevertheless, low l-BMAA concentrations (≥ 0.1mM, 48h) increased protein ubiquitination, 20S proteasomal and caspase 12 activity, expression of the endoplasmic reticulum (ER) stress marker CHOP, and enhanced phosphorylation of elf2α in SH-SY5Y cells. In contrast, high l-BMAA concentrations (≥ 1mM, 48h) increased reactive oxygen species and protein oxidization, which were partially ameliorated by coincubation with vitamin E. l-BMAA-mediated cytotoxicity was observable 48h following ≥ 2mM l-BMAA treatment. Consequently, the data presented here suggest that low l-BMAA concentrations result in a dysregulation of the cellular protein homeostasis with ensuing ER stress that is independent from high-concentration effects such as excitotoxicity and oxidative stress. Thus, the latter could be a contributing factor in the onset and slow progression of ALS/PDC in Guam. Stemmer, Kerstin deposit-license 2013-01 Stemmer, Kerstin Okle, Oliver Toxicological sciences ; 131 (2013), 1. - S. 217-224 Okle, Oliver eng 2014-07-31T14:48:44Z Deschl, Ulrich

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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