Abstract: Metallothionein (MT) protein and mRNA levels were monitored following exposure of rat neonatal primary astrocyte cultures to methylmercury (MeHg). MT‐I and MT‐II mRNAs were probed on northern blots with an [α‐32P]dCTP‐labeled synthetic cDNA probe specific for rat MT mRNA. MT‐I and MT‐II mRNAs were detected in untreated cells, suggesting constitutive MT expression in these cells. The probes hybridize to a single mRNA with a size appropriate for MT, ∼550 and 350 bp for MT‐I and MT‐II, respectively. Expression of MT‐I and MT‐II mRNA in astrocyte monolayers exposed to 2 × 10−6M MeHg for 6 h was increased over MT‐I and MT‐II mRNA levels in controls. Western blot analysis revealed a time‐dependent increase in MT protein synthesis through 96 h of exposure to MeHg. Consistent with the constitutive expression of MTs at both the mRNA level and the protein level, we have also demonstrated a time‐dependent increase in MT immunoreactivity in astrocytes exposed to MeHg. The cytotoxic effects of MeHg were measured by the rate of astrocytic d‐[3H]aspartate uptake. Preexposure of astrocytes to CdCl2, a potent inducer of MTs, completely reversed the inhibitory effect of MeHg on d‐[3H]aspartate uptake that occurs in MeHg‐treated astrocytes with constitutive MT levels. Associated with CdCl2 treatment was a time‐dependent increase in astrocytic MT levels. In summary, astrocytes constitutively express MTs; treatment with MeHg increases astrocytic MT expression, and increased MT levels (by means of CdCl2 pretreatment) attenuate MeHg‐induced toxicity. Increased MT expression may represent a generalized response to heavy metal exposure, thus protecting astrocytes and perhaps also, indirectly, juxtaposed neurons from the neurotoxic effects of heavy metals.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Neurochemistry|
|State||Published - Oct 1995|
- Cadmium chloride
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience