METALLOTHIONEIN INDUCTION PROTECTS SWOLLEN RAT PRIMARY ASTROCYTE CULTURES FROM METHYLMERCURY-INDUCED INHIBITION OF REGULATORY VOLUME DECREASE

Metallothionein (MT) proteins have been postulated to play a role in t he detoxification of heavy metals. Since methylmercury (MeHg) preferen tially accumulates in astrocytes, and MT-1 and MT-2 are astrocyte-spec ific MT isoforms, we investigated the ability of MTs to attenuate MeHg -induced cytotoxicity. The toxic effects of MeHg on astrocytes were in vestigated in a model of regulatory volume decrease (RVD) in which the cells are swollen by exposure to a hypotonic buffer. Preexposure to C dCl2 (1 mu M) for 72, 96 or 120 h, prior to acute exposure to hypotoni c buffer and MeHg (10 mu M) led to a time-dependent increase in the in tracellular levels of astrocyte MT proteins. The acute MeHg-induced in hibition of RVD was significantly, and almost fully reversed by preexp osure to CdCl2. This reversal was time-dependent, 120-h preexposure to CdCl2 producing the greatest reversibility. Furthermore, the ability of astrocytes to efficiently volume regulate in the presence of MeHg-c ontaining hypotonic buffer was highly correlated (r = 0.99) with the i ntracellular levels of MT proteins. The release of [H-3]taurine, an os molyte involved in the RVD process was also measured. The inhibitory e ffect of MeHg on [H-3]taurine in swollen cells was significantly, and fully reversed by CdCl2 preexposure. The study suggests that astrocyte s induced to express high levels of MT proteins are resistant to the a cute inhibitory effect of MeHg on RVD.