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 language | English |
|---|---|
| Pages (from-to) | 160-164 |
| Number of pages | 5 |
| Journal | Brain Research |
| Volume | 871 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 14 2000 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Molecular Biology
- Clinical Neurology
- Developmental Biology
Cite this
Involvement of caspase 3-like protease in methylmercury-induced apoptosis of primary cultured rat cerebral microglia. / Nishioku, Tsuyoshi; Takai, Nobuhiko; Miyamoto, Ken Ichiro; Murao, Koji; Hara, Chiaki; Yamamoto, Kenji; Nakanishi, Hiroshi.
In: Brain Research, Vol. 871, No. 1, 14.07.2000, p. 160-164.Research output: Contribution to journal › Article
}
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
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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UR - http://www.scopus.com/inward/citedby.url?scp=0034648117&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(00)02436-7
DO - 10.1016/S0006-8993(00)02436-7
M3 - Article
VL - 871
SP - 160
EP - 164
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -