title: Non-linear effects of cycloheximide in glutamate-treated cultured rat cerebellar neurons.
abstract: Multiple cell types and organisms across a wide array of phyla and a variety of toxins demonstrate non-linear dose responses to low-level chemical exposures with high doses inhibiting cellular function and low doses stimulating function. We tested whether such non-linear responses to low and ultra-low dose N-methyl-D-aspartate (NMDA), 1-methyl-4-phenylpyridinium (MPP+) or cycloheximide moderated toxic glutamate exposure in cultured cerebellar granule cells. Neurons were incubated over 72 h with successive NMDA, MPP+ iodide or cycloheximide additions producing specified low (10(-5), 10(-7), 10(-9), 10(-11), and 10(-13) M) and ultra-low (10(-27),10(-29), 10(-63), and 10(-65) M) concentrations. Subsequently these neuronal cells were exposed to a 50% excitotoxic concentration of glutamate for 24 h. Neuronal viability was significantly reduced in neurons treated with micromolar (10(-5) M) cycloheximide whereas viability was enhanced in neurons treated with an ultra-low dose exposure of 10(-27) M cycloheximide. Neither NMDA nor MPP+ elicited harmful or protective responses. This is the first report demonstrating non-linear dose-response effects of cycloheximide in low and ultra-low concentration ranges.
authors.affiliation: Samueli Institute for Informational Biology, Program on Neuroprotection and Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Marotta
authors.forename: Ann
authors.initials: A
authors.lastname: Marini
authors.forename: Krishna
authors.initials: K
authors.lastname: Banaudha
authors.forename: Susan
authors.initials: S
authors.lastname: Maharaj
authors.forename: John
authors.initials: J
authors.lastname: Ives
authors.forename: Craig R
authors.initials: CR
authors.lastname: Morrissette
authors.forename: Wayne B
authors.initials: WB
authors.lastname: Jonas
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D007928:Lethal Dose 50; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D017711:Nonlinear Dynamics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D018698:Glutamic Acid; D016202:N-Methylaspartate; D003513:Cycloheximide