FEBS Letters | |
Sorsby's fundus dystrophy mutant tissue inhibitors of metalloproteinase‐3 induce apoptosis of retinal pigment epithelial and MCF‐7 cells | |
Smith, Valerie A1  Majid, Mohammed A1  Newby, Andrew C3  Easty, David L1  Baker, Andrew H2  | |
[1] Institute of Ophthalmology, University of Bristol, Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK;Department of Medicine and Therapeutics, University of Glasgow, Glasgow G11 6NT, UK;Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Marlborough Road, Bristol BS2 8HW, UK | |
关键词: Tissue inhibitor of metalloproteinases; Apoptosis; Macular dystrophy; RPE; retinal pigment epithelium; SFD; Sorsby's fundus dystrophy; TIMP; tissue inhibitor of metalloproteinase; | |
DOI : 10.1016/S0014-5793(02)03359-8 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
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 overexpresion 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.
【 授权许可】
Unknown
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