PMID- 26888435 OWN - NLM STAT- MEDLINE DCOM- 20170125 LR - 20170125 IS - 1095-8355 (Electronic) IS - 1065-6995 (Linking) VI - 40 IP - 5 DP - 2016 May TI - Nuclear extrusion precedes discharge of genomic DNA fibers during tunicamycin-induced neutrophil extracellular trap-osis (NETosis)-like cell death in cultured human leukemia cells. PG - 597-602 LID - 10.1002/cbin.10594 [doi] AB - 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. CI - (c) 2016 International Federation for Cell Biology. FAU - Nakayama, Tomofumi AU - Nakayama T AD - Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto, 860-8555, Japan. FAU - Saitoh, Noriko AU - Saitoh N AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto , University, Kumamoto, Japan. FAU - Morotomi-Yano, Keiko AU - Morotomi-Yano K AD - Institute of Pulsed Power Science, Kumamoto , University, Kumamoto, Japan. FAU - Yano, Ken-Ichi AU - Yano K AD - Institute of Pulsed Power Science, Kumamoto , University, Kumamoto, Japan. FAU - Nakao, Mitsuyoshi AU - Nakao M AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto , University, Kumamoto, Japan. FAU - Saitoh, Hisato AU - Saitoh H AD - Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto, 860-8555, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160304 PL - England TA - Cell Biol Int JT - Cell biology international JID - 9307129 RN - 0 (Anti-Bacterial Agents) RN - 0 (DNA, Neoplasm) RN - 11089-65-9 (Tunicamycin) RN - 20350-15-6 (Brefeldin A) RN - 67526-95-8 (Thapsigargin) SB - IM MH - Anti-Bacterial Agents/pharmacology MH - Apoptosis/drug effects MH - Brefeldin A/pharmacology MH - Cell Death/drug effects MH - Cell Nucleus/metabolism MH - Cells, Cultured MH - DNA, Neoplasm/metabolism MH - Extracellular Traps/*metabolism MH - Glycosylation MH - HL-60 Cells MH - Humans MH - Leukemia/*drug therapy/genetics/metabolism/pathology MH - Neutrophils/metabolism MH - Thapsigargin/pharmacology MH - Tunicamycin/*pharmacology MH - Unfolded Protein Response/drug effects OTO - NOTNLM OT - cell death OT - extracellular chromatin OT - nucleus OT - tunicamycin EDAT- 2016/02/19 06:00 MHDA- 2017/01/26 06:00 CRDT- 2016/02/19 06:00 PHST- 2015/11/13 00:00 [received] PHST- 2016/02/14 00:00 [accepted] PHST- 2016/02/19 06:00 [entrez] PHST- 2016/02/19 06:00 [pubmed] PHST- 2017/01/26 06:00 [medline] AID - 10.1002/cbin.10594 [doi] PST - ppublish SO - Cell Biol Int. 2016 May;40(5):597-602. doi: 10.1002/cbin.10594. Epub 2016 Mar 4.