Inorganic mercury modifies Ca2+ signals, triggers apoptosis and potentiates NMDA toxicity in cerebellar granule neurons

Anna D. Rossi, Barbara Viviani, Boris Zhivotovsky, Luigi Manzo, Sten Orrenius, Marie Vahter, Pierluigi Nicotera

Research output: Contribution to journalArticlepeer-review

Abstract

Hg2+ (0.1 μM - 0.5 μM) modified the Ca2+ signals elicited by either KCI or the glutamate-receptor agonist, N-methyl-D-aspartate (NMDA), in cerebellar granule cells (CGCs), Hg2+ enhanced the intracellular Ca2+ transient elicited by high KC and prevented a complete recovery of the resting intracellular Ca2+ concentration ([Ca2+](i)) after either KCI or NMDA stimulation. Higher Hg2+ concentrations (up to 1 μM) 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 μM Hg2+ and a sublethal NMDA concentration (50 μM) 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.

Original languageEnglish
Pages (from-to)317-324
Number of pages8
JournalCell Death and Differentiation
Volume4
Issue number4
Publication statusPublished - May 1997

Keywords

  • Apoptosis
  • Calcium
  • Excitotoxicity
  • L-type channels

ASJC Scopus subject areas

  • Cell Biology

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