TY - JOUR
T1 - Involvement of caspase 3-like protease in methylmercury-induced apoptosis of primary cultured rat cerebral microglia
AU - Nishioku, Tsuyoshi
AU - Takai, Nobuhiko
AU - Miyamoto, Ken Ichiro
AU - Murao, Koji
AU - Hara, Chiaki
AU - Yamamoto, Kenji
AU - Nakanishi, Hiroshi
N1 - Funding Information:
This work was supported by Granti-in-Aid for Scientific Research Grants No. 11671845 (H.N.) from the Ministry of Education, Sciences, and Culture, Japan.
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2000/7/14
Y1 - 2000/7/14
N2 - 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.
AB - 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.
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U2 - 10.1016/S0006-8993(00)02436-7
DO - 10.1016/S0006-8993(00)02436-7
M3 - Article
C2 - 10882796
AN - SCOPUS:0034648117
VL - 871
SP - 160
EP - 164
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1
ER -