肝豆状核变性细胞溶酶体内外铜及铜结合蛋白的分布

DISTRIBUTION OF COPPER AND METALLOTHIONEIN INSIDE AND OUTSIDE OF LYSOSOMES IN THE CULTURED HEPATOLENTICULAR DEGENERATION CELLS

研究肝豆状该变性（HLD）的病理机制。以培养的皮肤成纤维细胞为模型，利用电镜X射线显微分析技术研究HLD不同等位基因组成及不同病程患者溶酶体内外铜、硫分布，并进行定量分析。结果：HLD早期患者细胞中溶酶体外的铜含量高于溶酶体内，而随病程延长，铜逐渐呈现溶酶体内分布的特点，且溶酶体外铜含量和硫含量呈正相关。杂合子和对照组溶酶体内外铜含量无显著差异。结论：溶酶体外存在含硫的铜结合蛋白，它和铜的结合降低了游离铜的毒性。细胞膜的铜转运ATP酶的缺陷可能是导致HLD一系列病理变化的根本原因。

PURPOSE To study the primary pathpgenesis of hepatolenticular degeneration (HLD).METHODS We originally used cultured fibroblasts as an in vitro model to invesigate the distribution of copper inside and outside of lysosomes of fibroblasts by the quantitative electim probe X-ray microanalysis.RESULTS The results revealed that copper outside of lysosomes is higher than tha inside lysosomes in HLD cells at early stage, while at late stage copper outside of lysosomes decrease and lysosomal deposits increase. Meanwhile copper is correlated with sulfur outside of lysosomes in HLD cells. There are no significant differences between outside and inside of lysosomes in heterozygote and control cells.CONCLUSIONS There is metallothionein outside of lysosome, it binds to coppet and may decrease the toxin of free copper. P-type ATPase plays an important role in the pathogensis of HLD.