Mr. Stein et Ld. Trombetta, EFFECTS OF DIETHYLDITHIOCARBAMATE ON CALMODULIN IN NEUROBLASTOMA-CELLS, Journal of toxicology and environmental health, 39(4), 1993, pp. 465-481
Diethyldithiocarbamate (DDC) was used to treat the neuroblastoma cell
line Neuro-2a. Cell injury caused by DDC affects the calcium-binding p
rotein calmodulin (CaM) and alters copper homeostasis in these cells.
Neuro-2a cells were treated with 1 x 10(-5) M DDC for 1 h and were har
vested at various time points over a 24-h period. Light microscopy of
control cells showed CaM deposited around the cell periphery and along
the neuritic processes. Treated cells showed the same distribution un
til 3 h after treatment. Electron microscopy showed CaM deposited arou
nd the cell periphery and within the cytoplasm and nucleus of control
cells. Treated cells showed a time-dependent localization of CaM in re
lation to cellular disorganization. Staining of electrophoretic transf
ers by ProtoGold showed that CaM was present in all control samples an
d treated samples through 6 h. Atomic absorption spectrophotometry sho
wed no difference in calcium levels between control and treated sample
s, but copper levels were significantly elevated. This study indicated
that degenerative changes induced by DDC altered calmodulin levels. T
hese changes may have been caused by elevated copper content within th
e cells and subsequent cell injury.