Effects of neurotoxins on neurone-specific enolase and lactate dehydrogenase activity and leakage in neuroblastoma cells.
Differentiation of the C1300 N2A (mouse) and IMR 32 (human) neuroblastoma cell lines with bromodeoxyuridine induces the expression of neurone-specific enolase (NSE). The expression of NSE is increased approximately three-fold on differentiation of the IMR 32 cells and two-fold in the C1300 cells. The amount of intracellular NSE and lactate dehydrogenase (LDH), and the release of these cytosolic proteins, was followed after exposure of differentiated IMR 32 cells to the neurotoxins 1-methyl-4-phenyl pyridinium (MPP(+;)) and kainic acid. After 48 hr of exposure to MPP(+;) (10(-8)m-10(-6)m) there was a concentration-dependent decrease in intracellular LDH and NSE. However, the amounts of these proteins measured in the medium suggested (i) that there was no concentration-related increase in cell death; and (ii) that the amounts in the medium reflected intracellular levels of these proteins. Data obtained previously showed that, after 24 hr exposure, these concentrations of neurotoxin caused changes in cellular protein degradation that were not accompanied by cell death. Several parameters of cellular protein metabolism show toxin-induced changes at low dose levels in the absence of concomitant cell death. Therefore, indices of deranged protein metabolism may provide sensitive markers of neurotoxicity.
Thomas
S M
SM
Division of Biological Sciences, School of Biological Sciences, Hatfield Polytechnic, College Lane, Hatfield, Herts. AL10 9AB, UK.
Hartley
C L
CL
Mason
H J
HJ