Acrylamide-induced effects on general and neurospecific cellular functions during exposure and recovery.
Basal cytotoxicity, morphological changes and alterations in cell physiological and neurochemical functions were studied in differentiated human neuroblastoma (SH-SY5Y) cells during exposure to acrylamide and during a subsequent recovery period after cessation of exposure. Acrylamide induced a 20% reduction in the number of neurites per cell at 0.21 mmol/L and 20% decrease in the protein synthesis rate at 0.17 mmol/L after 72 h of exposure. Furthermore, the basal level of intracellular calcium concentration ([Ca2+]i) and receptor-activated (carbachol, 0.1 mmol/L) Ca2+ fluxes increased by 49% and 21%, respectively, at 0.25 mmol/L. These observations were made at noncytotoxic acrylamide concentrations, signifying specific neurotoxic alterations. Forty-eight hours after cessation of acrylamide exposure, the SH-SY5Y cells had recovered, i.e., the number of neurites per cell as well as the basal level of [Ca2+]i and rate of protein synthesis were comparable to those of control cells. The general calpain inhibitor calpeptin decreased the acrylamide-induced (0.5 mmol/L) neurite degeneration, determined as reduction in number of neurites per cell, from 52% to 17% as compared to control cells, which further supports the hypothesis that an increased [Ca2+]i plays a significant role for acrylamide-induced axonopathy.
Nordin-Andersson
M
M
Stockholm University, Department of Neurochemistry and Neurotoxicology, Stockholm, Sweden.
Walum
E
E
Kjellstrand
P
P
Forsby
A
A
D020106:Acrylamide / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured
D009498:Neurotoxins; D020106:Acrylamide; D002217:Carbachol; D002118:Calcium