Metallothionein induction protects swollen rat primary astrocyte cultures from methylmercury-induced inhibition of regulatory volume decrease

Domenico Vitarella, Dawn R. Conklin, Harold K. Kimelberg, Michael Aschner

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Metallothionein (MT) proteins have been postulated to play a role in the detoxification of heavy metals. Since methylmercury (MeHg) preferentially accumulates in astrocytes, and MT-1 and MT-2 are astrocyte-specific MT isoforms, we investigated the ability of MTs to attenuate MeHg-induced cytotoxicity. The toxic effects of MeHg on astrocytes were investigated in a model of regulatory volume decrease (RVD) in which the cells are swollen by exposure to a hypotonic buffer. Preexposure to CdCl2 (1 μM) for 72, 96 or 120 h, prior to acute exposure to hypotonic buffer and MeHg (10 μM) led to a time-dependent increase in the intracellular levels of astrocyte MT proteins. The acute MeHg-induced inhibition of RVD was significantly, and almost fully reversed by preexposure 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-containing hypotonic buffer was highly correlated (r = 0.99) with the intracellular levels of MT proteins. The release of [3H]taurine, an osmolyte involved in the RVD process was also measured. The inhibitory effect of MeHg on [3H]taurine in swollen cells was significantly, and fully reversed by CdCl2 preexposure. The study suggests that astrocytes induced to express high levels of MT proteins are resistant to the acute inhibitory effect of MeHg on RVD.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalBrain Research
Volume738
Issue number2
DOIs
StatePublished - Nov 4 1996
Externally publishedYes

Keywords

  • astrocyte
  • hypotonicity
  • metallothionein
  • methylmercury
  • regulatory volume decrease
  • taurine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Metallothionein induction protects swollen rat primary astrocyte cultures from methylmercury-induced inhibition of regulatory volume decrease'. Together they form a unique fingerprint.

  • Cite this