Inhibition of deoxyribonuclease I by actin is to protect cells from premature cell death
Inhibition of deoxyribonuclease I by actin is to protect cells from premature cell death
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DOI：
10.1007/s10495-007-0078-4
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发表时间：
2007-08-01
期刊：
影响因子：
7.2
通讯作者：
Mannherz, Hans Georg
中科院分区：
文献类型：
--
作者：
Eulitz, Dirk;Mannherz, Hans Georg
脱氧核糖核酸酶I（Dnase 1）是主要的胞外核酸内切酶。它由消化腺分泌到消化道中，并分别由肝细胞、泪腺和肾近端小管细胞分泌到血浆、泪液和尿液中。在许多物种中，DNase 1的活性被单体肌动蛋白抑制。然而，这种高亲和力相互作用的生物学意义是未知的。我们产生了一个Dnase 1突变体，肌动蛋白结合能力大大降低。将野生型和突变型Dnase 1的EGFP构建体转染入MCF-7乳腺癌细胞，并通过星形孢菌素或氧化应激诱导凋亡或坏死。在细胞凋亡过程中，更快的染色质断裂发生在细胞转染突变体DNase 1。当野生型（野生型）或突变的DNA酶1被添加到细胞诱导坏死后，更快的染色质降解发生在突变的DNA酶1的存在下。列入肌动蛋白在这些条件下抑制染色质降解的wt-，但不是由突变的DNase 1。因此，肌动蛋白对DNase 1的抑制可能是细胞损伤过程中防止DNA过早降解的一种自我保护机制。
Deoxyribonuclease I (Dnase1) is the major extracellular endonuclease. It is secreted by digestive glands into the alimentary tract and into the plasma, lacrimal fluid and urine by hepatocytes, lacrimal glands and renal proximal tubular cells, respectively. In many species the activity of Dnase1 is inhibited by monomeric actin. However, the biological significance of this high affinity interaction is unknown. We generated a Dnase1 mutant with extremely reduced actin binding capacity. EGFP-constructs of wild-type and mutant Dnase1 were transfected into MCF-7 breast cancer cells and apoptosis or necrosis was induced by staurosporine or oxidative stress. During apoptosis faster chromatin fragmentation occurred in cells transfected with mutant Dnase1. When wt (wildtype)or mutated Dnase1 were added to cells after induction of necrosis, faster chromatin degradation occurred in the presence of mutant Dnase1. Inclusion of actin under these conditions inhibited chromatin degradation by wt-but not by mutated Dnase1. Thus, inhibition of Dnase1 by actin may serve as a self-protection mechanism against premature DNA degradation during cell damage.