In vitro studies of acrylamide neurotoxicity in rat pheochromocytoma (PC12) cells

By Lin, W.W. - Johnson, L.R. - Friedman, M.A. - Abou-Donia, M.B.

This review discusses our studies on molecular mechanisms of acrylamide neurotoxicity by using the rat pheochromocytoma (PC12) cell line. The results showed that: a) acrylamide altered the gross morphology of PC12 cells; b) acrylamide induced neurofilament accumulation in PC12 cells; C) the effects of acrylamide on PC12 cells are consistent with its neurotoxicity in vivo; d) acrylamide stimulated neurofilament protein 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 differentially regulated the mRNA levels of three neurofilament subunit genes 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) acrylamide may differentially regulate the expression of each subunit, resulting in aberrant accumulation of neurofilament proteins; and c) there is a dexamethasone-sensitive signalling step common to NGF and acrylamide. These results could partially explain the mechanisms of neurofilament accumulation in distal axonal swellings, a pathognomonic feature of acrylamide neurotoxicity.