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2014 ; 5
(10
): e1494
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Caspase-dependent cell death-associated release of nucleosome and
damage-associated molecular patterns
#MMPMID25356863
Yoon S
; Park SJ
; Han JH
; Kang JH
; Kim JH
; Lee J
; Park S
; Shin HJ
; Kim K
; Yun M
; Chwae YJ
Cell Death Dis
2014[Oct]; 5
(10
): e1494
PMID25356863
show ga
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.