کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2569676 | 1128544 | 2012 | 8 صفحه PDF | دانلود رایگان |

The neuroblastoma–spinal motor neuron fusion cell line, NSC-34, in its differentiated form, NSC-34D, permits examining the effects of riluzole, a proven treatment for amyotrophic lateral sclerosis (ALS) on cell death induction by staurosporine (STS), thapsigargin (Thaps), hydrogen peroxide (H2O2) and homocysteine (HCy). These neurotoxins, applied exogenously, have mechanisms of action related to the various proposed molecular pathogenetic pathways in ALS and are differentiated from endogenous cell death that is associated with cytoplasmic aggregate formation in motor neurons. Nuclear morphology, caspase-3/7 activation and high content imaging were used to assess toxicity of these neurotoxins with and without co-treatment with riluzole, a benzothiazole compound with multiple pharmacological actions. STS was the most potent neurotoxin at killing NSC-34D cells with a toxic concentration at which 50% of maximal cell death is achieved (TC50 = 0.01 μM), followed by Thaps (TC50 = 0.9 μM) and H2O2 (TC50 = 15 μM) with HCy requiring higher concentrations to kill at the same level (TC50 = 2200 μM). Riluzole provided neurorescue with a 20% absolute reduction (47.6% relative reduction) in apoptotic cell death against Thaps-induced NSC-34D cell (p ≤ 0.05), but had no effect on STS-, H2O2- and HCy-induced NSC-34D cell death. This effect of riluzole on Thaps induction of cell death was independent of caspase-3/7 activation. Riluzole mitigated a toxin that can cause intracellular calcium dysregulation associated with endoplasmic reticulum (ER) stress but not toxins associated with other cell death mechanisms.
► Calcium-dependent neurotoxins are potent cell death inducers in NSC-34D cells.
► Riluzole provides neurorescue against Thaps-induced NSC-34D cell death.
► Riluzole had no effect on neurotoxicity by STS, H2O2 and Hcy.
► Riluzole reduces NSC-34D cell death independent of caspase-3/7 activation.
Journal: Toxicology and Applied Pharmacology - Volume 258, Issue 2, 15 January 2012, Pages 208–215