Involvement of caspase 3-like protease in methylmercury-induced apoptosis of primary cultured rat cerebral microglia

Tsuyoshi Nishioku, Nobuhiko Takai, Ken Ichiro Miyamoto, Koji Murao, Chiaki Hara, Kenji Yamamoto, Hiroshi Nakanishi

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42 Citations (Scopus)

Abstract

Methylmercury (MeHg) has been implicated to induce massive neurodegeneration by disruption of neuron-glia interactions besides a direct potent neurotoxicity. In the present study, we examined potential cytotoxic effects of MeHg on primary cultured rat microglia. Following treatment with a relatively low concentration (0.5 μM) of MeHg, microglia had induced cell death accompanied by DNA fragmentation and an activation of caspase-3-like protease. MeHg-induced microglial death was significantly suppressed by the caspase-3-like protease inhibitor benzyloxycarbonyl-Try-Val-Ala-Asp-fluoromethyl-ketone indicating the occurrence of caspase-3-like protease-executed apoptosis. The aspartic protease inhibitor pepstatin A had a partial but significant inhibitory effect on MeHg-induced microglial apoptosis. These results indicate that a relatively low concentration of MeHg predominantly induces caspase-3-like protease-executed apoptosis of microglia, while the endosomal/lysosomal system is also partially involved in the cell death pathway. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)160-164
Number of pages5
JournalBrain Research
Volume871
Issue number1
DOIs
Publication statusPublished - Jul 14 2000

All Science Journal Classification (ASJC) codes

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

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