Degradation of nuclear DNA by DNase II-like acid DNase in cortical fiber cells of mouse eye lens
Degradation of nuclear DNA by DNase II-like acid DNase in cortical fiber cells of mouse eye lens
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DOI：
10.1111/j.1742-4658.2007.05836.x
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发表时间：
2007-07-01
期刊：
影响因子：
5.4
通讯作者：
Nagata, Shigekazu
中科院分区：
文献类型：
--
作者：
Nakahara, Masaki;Nagasaka, Akiomi;Nagata, Shigekazu
晶状体由纤维细胞组成，纤维细胞与晶状体前表面的上皮细胞不同。与这种分化相一致的是，晶状体功能必需的一组蛋白质被合成，细胞器被降解。类似DNA酶II的酸性DNA酶，也称为DNA酶II β，在晶状体中特异性表达，并降解晶状体纤维细胞中的DNA。在这里，我们报道了dna酶ii样酸性dna酶作为具有信号序列的前体合成，并且定位于溶酶体。在皮质纤维细胞中发现了DNase ii样酸性DNase mRNA，而在上皮细胞中没有发现，表明其表达是在上皮细胞向纤维细胞分化的过程中被诱导的。免疫组织化学和免疫细胞化学分析表明，DNase ii样酸性DNase与Lamp-1共定位于纤维细胞的溶酶体中，位于与无细胞器区接壤的相对狭窄的区域，并且经常在变性细胞核中发现。通过微阵列分析比较了幼鼠晶状体上皮细胞和皮层纤维细胞的基因表达谱，发现溶酶体酶（组织蛋白酶和脂肪酶）的一些基因在纤维细胞中强烈表达。这些结果表明，在晶状体细胞分化过程中，溶酶体系统在细胞器的降解中起作用。
The eye lens is composed of fiber cells that differentiate from epithelial cells on its anterior surface. In concert with this differentiation, a set of proteins essential for lens function is synthesized, and the cellular organelles are degraded. DNase II-like acid DNase, also called DNase II beta, is specifically expressed in the lens, and degrades the DNA in the lens fiber cells. Here we report that DNase II-like acid DNase is synthesized as a precursor with a signal sequence, and is localized to lysosomes. DNase II-like acid DNase mRNA was found in cortical fiber cells but not epithelial cells, indicating that its expression is induced during the differentiation of epithelial cells into fiber cells. Immunohistochemical and immunocytochemical analyses indicated that DNase II-like acid DNase was colocalized with Lamp-1 in the lysosomes of fiber cells in a relatively narrow region bordering the organelle-free zone, and was often found in degenerating nuclei. A comparison by microarray analysis of the gene expression profiles between epithelial and cortical fiber cells of young mouse lens indicated that some genes for lysosomal enzymes (cathepsins and lipases) were strongly expressed in the fiber cells. These results suggest that the lysosomal system plays a role in the degradation of cellular organelles during lens cell differentiation.