索斯比眼底营养不良突变型金属蛋白酶组织抑制剂-3诱导视网膜色素上皮细胞和MCF-7细胞凋亡。

Sorsby's fundus dystrophy mutant tissue inhibitors of metalloproteinase-3 induce apoptosis of retinal pigment epithelial and MCF-7 cells.

作者信息

Majid Mohammed A, Smith Valerie A, Easty David L, Baker Andrew H, Newby Andrew C

机构信息

Institute of Ophthalmology, University of Bristol, Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK.

出版信息

FEBS Lett. 2002 Oct 9;529(2-3):281-5. doi: 10.1016/s0014-5793(02)03359-8.

DOI:10.1016/s0014-5793(02)03359-8

PMID:12372614

Abstract

C-terminal domain tissue inhibitor of metalloproteinases-3 (TIMP-3) mutations cause the rare hereditary blindness Sorsby's fundus dystrophy (SFD), which involves loss of retinal pigment epithelial (RPE) cells. Since wild-type TIMP-3 causes apoptosis, we investigated whether SFD TIMP-3 might kill RPE and other cells. Plasmid-mediated overexpression of Ser-156, Gly-167, Tyr-168 and Ser-181 SFD mutant TIMP-3 decreased RPE viability to 22+/-8, 20+/-6, 32+/-5, 30+/-12% (SFD mutants all P<0.01 versus wild-type 50+/-8%) and similarly increased propidium iodide staining and in situ end labelling. Adenovirus-mediated overexpression of the Gly-167 mutant also caused RPE apoptosis dose-dependently. Apoptosis of RPE cells might therefore contribute to the pathology of SFD.

摘要

金属蛋白酶组织抑制剂-3（TIMP-3）的C末端结构域突变会导致罕见的遗传性失明——索斯比眼底营养不良（SFD），该病涉及视网膜色素上皮（RPE）细胞的丧失。由于野生型TIMP-3会导致细胞凋亡，我们研究了SFD TIMP-3是否会杀死RPE细胞和其他细胞。质粒介导的Ser-156、Gly-167、Tyr-168和Ser-181 SFD突变型TIMP-3的过表达使RPE细胞活力降至22±8%、20±6%、32±5%、30±12%（所有SFD突变体与野生型50±8%相比，P均<0.01），并同样增加了碘化丙啶染色和原位末端标记。腺病毒介导的Gly-167突变体的过表达也剂量依赖性地导致RPE细胞凋亡。因此，RPE细胞凋亡可能是SFD发病机制的一部分。