title: Inorganic mercury modifies Ca2+ signals, triggers apoptosis and potentiates NMDA toxicity in cerebellar granule neurons.
abstract: Hg2+ (0.1 microM-0.5 microM) modified the Ca2+ signals elicited by either KCl or the glutamate-receptor agonist, N-methyl-D-aspartate (NMDA), in cerebellar granule cells (CGCs). Hg2+ enhanced the intracellular Ca2+ transient elicited by high K+ and prevented a complete recovery of the resting intracellular Ca2+ concentration ([Ca2+]i) after either KCl or NMDA stimulation. Higher Hg2+ concentrations (up to 1 microM) increased [Ca2+]i directly. Following the short-term exposure to Hg2+, CGCs underwent apoptosis, which was identified by the cleavage of DNA into large (700-50 kbp) and oligonucleosomal DNA fragments, and by the appearance of typical apoptotic nuclei. Combined treatment with 0.1-0.3 microM Hg2+ and a sublethal NMDA concentration (50 microM) potentiated DNA fragmentation and apoptotic cell death. When the exposure to Hg2+ was carried out in Ca2+-free media or in the presence of Ca2+ channel blockers (L-type or NMDA-R antagonists), the effects on signalling and apoptosis were prevented. Our results suggest that very low Hg2+ concentrations can trigger apoptosis in CGCs by facilitating Ca2+ entry through membrane channels.
authors.affiliation: Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A D
authors.initials: AD
authors.lastname: Rossi
authors.forename: B
authors.initials: B
authors.lastname: Viviani
authors.forename: B
authors.initials: B
authors.lastname: Zhivotovsky
authors.forename: L
authors.initials: L
authors.lastname: Manzo
authors.forename: S
authors.initials: S
authors.lastname: Orrenius
authors.forename: M
authors.initials: M
authors.lastname: Vahter
authors.forename: P
authors.initials: P
authors.lastname: Nicotera