title: Nuclear extrusion precedes discharge of genomic DNA fibers during tunicamycin-induced neutrophil extracellular trap-osis (NETosis)-like cell death in cultured human leukemia cells.
abstract: We previously reported that the nucleoside antibiotic tunicamycin (TN), a protein glycosylation inhibitor triggering unfolded protein response (UPR), induced neutrophil extracellular trap-osis (NETosis)-like cellular suicide and, thus, discharged genomic DNA fibers to extracellular spaces in a range of human myeloid cell lines under serum-free conditions. In this study, we further evaluated the effect of TN on human promyelocytic leukemia HL-60 cells using time-lapse microscopy. Our assay revealed a previously unappreciated early event induced by TN-exposure, in which, at 30-60 min after TN addition, the cells extruded their nuclei into the extracellular space, followed by discharge of DNA fibers to form NET-like structures. Intriguingly, neither nuclear extrusion nor DNA discharge was observed when cells were exposed to inducers of UPR, such as brefeldin A, thapsigargin, or dithiothreitol. Our findings revealed novel nuclear dynamics during TN-induced NETosis-like cellular suicide in HL-60 cells and suggested that the toxicological effect of TN on nuclear extrusion and DNA discharge was not a simple UPR.
authors.affiliation: Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto, 860-8555, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto , University, Kumamoto, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Saitoh
authors.affiliation: Institute of Pulsed Power Science, Kumamoto , University, Kumamoto, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Morotomi-Yano
authors.affiliation: Institute of Pulsed Power Science, Kumamoto , University, Kumamoto, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yano
authors.affiliation: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto , University, Kumamoto, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakao
authors.affiliation: Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto, 860-8555, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Saitoh
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020126:Brefeldin A / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000378:metabolism; D065206:Extracellular Traps / Q000378:metabolism*; D006031:Glycosylation; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology*; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004273:DNA, Neoplasm; D014415:Tunicamycin; D020126:Brefeldin A; D019284:Thapsigargin
keywords: cell death; extracellular chromatin; nucleus; tunicamycin