Lipopolysaccharide treatment arrests the cell cycle of BV-2 microglial cells in G1 phase and protects them from UV light-induced apoptosis

Lipopolysaccharide treatment arrests the cell cycle of BV-2 microglial cells in G1 phase and protects them from UV light-induced apoptosis
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DOI:
10.1007/s00702-014-1256-5
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发表时间:
2015-02-01
影响因子:
3.3
通讯作者:
Nagatsu, Toshiharu
Nagatsu, Toshiharu
中科院分区:
医学3区
文献类型:
--
作者:
Kaneko, Yoko S.;Ota, Akira;Nagatsu, Toshiharu

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We previously reported that an optimal dose of lipopolysaccharide (LPS) markedly extends the lifespan of murine primary-cultured microglia by suppressing cell death pathways. In this study, we investigated the effects of LPS pretreatment on UV light-induced apoptosis of cells from the microglial cell line BV-2. More than half of BV-2 cells were apoptotic, and procaspase-3 was cleaved into its active form at 3 h of UV irradiation. In contrast, in BV-2 cells treated with LPS for 24 h, UV irradiation caused neither apoptosis nor procaspase-3 cleavage. LPS treatment arrested the cell cycle in G(1) phase and upregulated cyclin-dependent kinase inhibitor p21(Waf1/Cip1) and growth arrest and DNA damage-inducible (GADD) 45 alpha in BV-2 cells. When p21(Waf1/Cip1) and GADD45 alpha were knocked down by small interfering RNA, procaspase-3 was cleaved into its active form to induce apoptosis. Our findings suggest that LPS inhibits UV-induced apoptosis in BV-2 cells through arrest of the cell cycle in G(1) phase by upregulation of p21(Waf1/Cip1) and GADD45 alpha. Excessive activation of microglia may play a critical role in the exacerbation of neurodegeneration, therefore, normalizing the precise regulation of apoptosis may be a new strategy to prevent the deterioration caused by neurodegenerative disorders.