Abstract: In the trisomy 16 mouse the increased gene dosage of SOD-1 increases
H2O2 production that results in increased oxidative stress. We report here that
in hippocampal primary cultures, metallothionein (MT)-I/II immunoreactivity was
present mainly in glial fibrillary acidic protein-immunolabeled cells. Western
blot analysis showed a two-fold higher level of MT-I/II in trisomy 16 mice then
in euploid littermates. In contrast, the immunoreactivity of glutamine
synthetase, another glia-expressed protein, was similar in hippocampal
cultures of trisomy 16 mouse and euploid littermates. Oxyblot analysis of
hippocampal cultures showed that the carbonyl content in several protein bands
was higher in trisomy 16 mice than in euploid littermates giving evidence for
increased oxidative stress in trisomy 16 mouse cultures. To evaluate the
responsiveness of MT-I/II to agents that increase the level of reactive oxygen
species in cells we measured the effect of H2O2, kainic acid, (±) ACPD, and
B-amyloid peptide 1-42. Western blot analysis documented that in hippocampal
cultures of euploid littermates MT-I/II was maximally increased by 50 µM H2O2,
100 µM kainic acid, 10 µM (±)ACPD, or 1.0 mM B-amyloid peptide 1-42, whereas
in those of trisomy 16 mice no furter increase above the elevated level was
observed. Our data suggest that in the trisomy 16 mouse the production of
reactive oxygen species may have shifted the intracellular redox environment
that could have alerted the susceptibility of MT-I/II transcription. The
possibilty that transcription factors whose activation may be essential to
initiate MT-I/II transcription get oxidized has yet to be examined.
