title: Caspase-dependent cell death-associated release of nucleosome and damage-associated molecular patterns.
abstract: Apoptosis, which is anti-inflammatory, and necrosis, which is pro-inflammatory, represent the extremes of the cell death spectrum. Cell death is complex and both apoptosis and necrosis can be observed in the same cells or tissues. Here, we introduce a novel combined mode of cellular demise--caspase-dependent regulated necrosis. Most importantly, it is mainly characterized with release of marked amount of oligo- or poly-nucleosomes and their attached damage-associated molecular patterns (DAMPs) and initiated by caspase activation. Caspase-activated DNase has dual roles in nucleosomal release as it can degrade extracellularly released chromatin into poly- or oligo-nucleosomes although it prohibits release of nucleosomes. In addition, osmotically triggered water movement following Cl(-) influx and subsequent Na(+) influx appears to be the major driving force for nucleosomal and DAMPs release. Finally, Ca(2+)-activated cysteine protease, calpain, is an another essential factor in nucleosomal and DAMPs release because of complete reversion to apoptotic morphology from necrotic one and blockade of nucleosomal and DAMPs release by its inhibition.
authors.affiliation: 1] Department of Microbiology, Ajou University School of Medicine, Suwon, Korea [2] Department of Biomedical Sciences, Ajou University, Suwon, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Yoon
authors.affiliation: 1] Department of Microbiology, Ajou University School of Medicine, Suwon, Korea [2] Department of Biomedical Sciences, Ajou University, Suwon, Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Pathology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Han
authors.affiliation: 1] Department of Microbiology, Ajou University School of Medicine, Suwon, Korea [2] Department of Biomedical Sciences, Ajou University, Suwon, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Electron Microscopy Laboratory, Eulji University, Seongnam, Korea.
authors.forename: J-h
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Bio-Medical Science Co. Ltd, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: 1] Department of Microbiology, Ajou University School of Medicine, Suwon, Korea [2] Department of Biomedical Sciences, Ajou University, Suwon, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.affiliation: 1] Department of Microbiology, Ajou University School of Medicine, Suwon, Korea [2] Department of Biomedical Sciences, Ajou University, Suwon, Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: 1] Department of Microbiology, Ajou University School of Medicine, Suwon, Korea [2] Department of Biomedical Sciences, Ajou University, Suwon, Korea.
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: M
authors.initials: M
authors.lastname: Yun
authors.affiliation: 1] Department of Microbiology, Ajou University School of Medicine, Suwon, Korea [2] Department of Biomedical Sciences, Ajou University, Suwon, Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Chwae
mesh_terms: D000596:Amino Acids / Q000172:deficiency; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D045744:Cell Line, Tumor; D018118:Chloride Channels / Q000378:metabolism; D004249:DNA Damage; D003851:Deoxyribonucleases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism* / Q000648:ultrastructure; D051192:Receptors, Pattern Recognition / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D018118:Chloride Channels; D009707:Nucleosomes; D051192:Receptors, Pattern Recognition; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease; D002154:Calpain; D020169:Caspases