Previously, the lab has shown that selenium toxicity caused a reduction in the number of eggs laid, reduced percentage of egg hatching and decreased adult survival in Caenorhabditis elegans, which corresponds to the published effects of selenium toxicity in livestock and wildlife. Here, we show that adult death appears to be associated with neuronal damage. Using animals expressing an
unc-119::gfp reporter construct, neuronal swelling and loss of chromatin staining was noted. These results correspond to published reports linking high environmental selenium to increased incidence of the motor neuron disease amyotrophic lateral sclerosis. Despite the well established toxic effects of selenium on neurons, little is known of the resulting aberrant cellular signaling. Cell culture studies have reported that selenomethionine and selenite can stimulate ERK while selenite inhibits the JNK and
p38 signaling pathways. Further,
jnk-1/jkk-1/mek-1 has been implicated in C. elegans response to stress and heavy metals. Several MAP kinase mutants (
sek-1 (AU1),
mek-1(FK171),
jkk-1 (KU2),
mpk-1 (MH37),
jnk-1 (VC8),
mpk-1 gf (PJ726)) were selected and screened for resistance/sensitivity to the lab"s previously defined selenium toxicity protocol (5mM sodium selenite). Preliminary results show that none of the mutants tested are resistant to selenium toxicity. Interestingly, comparison of
mpk-1 gain of function versus
mpk-1 loss of function showed that the
mpk-1 gain of function mutants were more sensitive to selenium toxicity than loss of function mutants. These results suggest a distinct stress-induced kinase cascade is part of selenium induced toxic processes.