Metal binding of metallothioneins in human astrocytomas (U87 MG, IPDDC-2A)

Abstract

Astroglia cells structurally and nutritionally support neurons in the central nervous system. They play an important role in guiding the construction of the nervous system and controlling the chemical and ionic environment of neurons. They also represent the major sites for accumulation and immobilisation of toxic metal ions most probably connected with metallothioneins. For this reason astroglia cells possess high cytosolic levels of metallothioneins I, II and III (MT-I,II,III). Our aim was to establish the inducibility and metal binding of MTs in two human astrocytoma cell lines, U87 MG (astrocytoma-glioblastoma, grade IV) and IPDDC-2A (astrocytoma, grade II), on exposure to cadmium chloride (1 microM). MTs were identified by molecular weight (size exclusion chromatography) and their metal content (Cd, Zn and Cu) to follow the interactions between metals. We showed that MTs are constitutively expressed in both human astrocytoma cell lines. In accordance with the higher malignancy grade of U87 MG, the amount of MTs was higher in U87 MG than in IPDDC-2A cells. After 24 hours of exposure to Cd their expression greatly increased in both cell lines and they were capable of immobilising almost all water soluble Cd. Induction of MTs in U87 MG cells was additionally followed up to 48 hours with exposure to different concentrations of CdCl(2) (1, 10 microM). Induction was a time dependent process throughout the period. Isoform III (identified by chromatographic separation of isoform III from I/II) was present at all exposure times, but only in traces with respect to the prevailing amounts of MT-I/II isoforms. So induction can be attributed to isoform I/II only.

Early immune response of neuronal cells (U87) to heavy metal Cd or Pb exposure

“…Further, Cd-treated nerve cells show marked changes in morphology and an increase in necrotic cells, eventually causing apoptosis [14]. In cell culture experiments, astrocytes are more resistant to acute high-doses of Cd (300 μM for 30 min) than neurons but more sensitive than neurons to long-term low-doses (10 μM) [15]. Significant decreases in cell viability have been observed with low micromolar Cd concentrations [16].…”

Elemental Mercury Exposure and Sleep Disorder

“…It is then oxidized in brain cells and complexed to the SH-group of the cell (Hursh et al, 1988;Magos et al, 1978). The divalent ionic Hg++ accumulates primarily in astrocytes, where it mostly binds to reduced glutathione (GSH), cystein, and metallothioneins (MTs) (Aschner, 1997;Tušek-Žnidarič et al, 2007). After Hg° vapour exposure of animals, a marked accumulation of Hg was observed in the cerebellum, nucleus olivarius inferior in the brainstem, and in the nucleus subtalamicus (Berlin et al, 1969).…”