IN-VITRO STUDIES OF ACRYLAMIDE NEUROTOXICITY IN RAT PHEOCHROMOCYTOMA (PC12) CELLS

This review discusses our studies on molecular mechanisms of acrylamid e neurotoxicity by using the rat pheochromocytoma (PC12) cell line. Th e results showed that: a) acrylamide altered the gross morphology of P C12 cells; b) acrylamide induced neurofilament accumulation in PC12 ce lls; c) the effects of acrylamide on PC12 cells are consistent with it s neurotoxicity in vivo; d) acrylamide stimulated neurofilament protei n synthesis in PC12 cells; e) acrylamide did not act via nerve growth factor (NGF) receptor gp140trk to regulate neurofilament synthesis in PC12 cells; f) dexamethasone antagonised NGF and/or acrylamide-induced neurofilament protein synthesis and expression; and g) acrylamide dif ferentially regulated the mRNA levels of three neurofilament subunit g enes in PC12 cells. These molecular studies provide the first evidence that: a) there are distinctive and convergent signalling pathways for NGF-regulated and acrylamide-regulated neurofilament expression; b) a crylamide may differentially regulate the expression of each subunit, resulting in aberrant accumulation of neurofilament proteins; and c) t here is a dexamethasone-sensitive signalling step common to NGF and ac rylamide. These results could partially explain the mechanisms of neur ofilament accumulation in distal axonal swellings, a pathognomonic fea ture of acrylamide neurotoxicity.