Mizuta Ryushin, Araki Shinsuke, Furukawa Makoto, Furukawa Yuki, Ebara Syota, Shiokawa Daisuke, Hayashi Katsuhiko, Tanuma Sei-ichi, Kitamura Daisuke
Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
PLoS One. 2013 Dec 2;8(12):e80223. doi: 10.1371/journal.pone.0080223. eCollection 2013.
Apoptosis and necrosis, two major forms of cell death, can be distinguished morphologically and biochemically. Internucleosomal DNA fragmentation (INDF) is a biochemical hallmark of apoptosis, and caspase-activated DNase (CAD), also known as DNA fragmentation factor 40 kDa (DFF40), is one of the major effector endonucleases. DNase γ, a Mg(2+)/Ca(2+)-dependent endonuclease, is also known to generate INDF but its role among other apoptosis-associated endonucleases in cell death is unclear. Here we show that (i) INDF occurs even during necrosis in cell lines, primary cells, and in tissues of mice in vivo, and (ii) DNase γ, but not CAD, is the effector endonuclease for INDF in cells undergoing necrosis. These results document a previously unappreciated role for INDF in necrosis and define its molecular basis.
凋亡和坏死是细胞死亡的两种主要形式，可从形态学和生物化学角度加以区分。核小体间DNA片段化（INDF）是凋亡的生化标志，而半胱天冬酶激活的脱氧核糖核酸酶（CAD），也称为40 kDa DNA片段化因子（DFF40），是主要的效应核酸内切酶之一。脱氧核糖核酸酶γ是一种依赖Mg(2+)/Ca(2+)的核酸内切酶，已知它也能产生INDF，但它在细胞死亡中与其他凋亡相关核酸内切酶相比的作用尚不清楚。在此我们表明：（i）在细胞系、原代细胞以及小鼠体内组织的坏死过程中也会发生INDF；（ii）在经历坏死的细胞中，脱氧核糖核酸酶γ而非CAD是INDF的效应核酸内切酶。这些结果证明了INDF在坏死中以前未被认识到的作用，并确定了其分子基础。
