title: Lipopolysaccharide treatment arrests the cell cycle of BV-2 microglial cells in G₁ phase and protects them from UV light-induced apoptosis.
abstract: 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 G1 phase and upregulated cyclin-dependent kinase inhibitor p21(Waf1/Cip1) and growth arrest and DNA damage-inducible (GADD) 45α in BV-2 cells. When p21(Waf1/Cip1) and GADD45α 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 G1 phase by upregulation of p21(Waf1/Cip1) and GADD45α. 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.
authors.affiliation: Department of Physiology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan, ykaneko@fujita-hu.ac.jp.
authors.forename: Yoko S
authors.initials: YS
authors.lastname: Kaneko
authors.forename: Akira
authors.initials: A
authors.lastname: Ota
authors.forename: Akira
authors.initials: A
authors.lastname: Nakashima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagasaki
authors.forename: Yu
authors.initials: Y
authors.lastname: Kodani
authors.forename: Keiji
authors.initials: K
authors.lastname: Mori
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Nagatsu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects* / Q000528:radiation effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000528:radiation effects; D020411:Oligonucleotide Array Sequence Analysis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000494:pharmacology; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008070:Lipopolysaccharides; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053148:Caspase 3