DNase , DNase I and caspase-activated DNase cooperate to degrade dead cells

作者：Koyama Ryo; Arai Tomoya; Kijima Marie; Sato Shoko; Miura Shigetoshi; Yuasa Makoto; Kitamura Daisuke; Mizuta Ryushin^*

来源：Genes to Cells, 2016, 21(11): 1150-1163.

DOI：10.1111/gtc.12433

Serum endonucleases are essential for degrading the chromatin released from dead cells and preventing autoimmune diseases such as systemic lupus erythematosus. Serum DNase I is known as the major endonuclease, but recently, another endonuclease, DNase /DNase I-like 3, gained attention. However, the precise role of each endonuclease, especially that of DNase , remains unclear. In this study, we distinguished the activities of DNase from those of DNase I in mouse serum and concluded that both cooperated in degrading DNA during necrosis: DNase functions as the primary chromatolytic activity, causing internucleosomal DNA fragmentation, and DNase I as the secondary one, causing random DNA digestion for its complete degradation. These results were confirmed by two invivo experimental mouse models, in which necrosis was induced, acetaminophen-induced hepatic injury and streptozotocin-induced -cell necrosis models. We also determined that DNase functions as a backup endonuclease for caspase-activated DNase (CAD) in the secondary necrosis phase after -ray-induced apoptosis invivo.

• 出版日期2016-11