Abstract：
AIM:Filamin binding LIM protein 1, also known as migfilin, is a skeleton organization protein that binds to mitogen-inducible gene 2 at cell-extracellular matrix adhesions. The aim of this study was to investigate the role of migfilin in cisplatin-induced apoptosis in human glioma cells, to determine the functional domains of migfilin, and to elucidate the molecular mechanisms underlying the regulation of cisplatin-related chemosensitivity. METHODS:The human glioma cell lines Hs683, H4, and U-87 MG were transfected with pEGFP-C2-migfilin to elevate the expression level of migfilin. RNA interference was used to reduce the expression of migfilin. To determine the functional domains of migfilin, U-87 MG cells were transfected with plasmids of migfilin deletion mutants. After treatment with cisplatin (40 μmol/L) for 24 h, the cell viability was assessed using the MTS assay, and the cell apoptotic was examined using the DAPI staining assay and TUNEL analysis. Expression levels of apoptosis-related proteins were detected by Western blot analysis. RESULTS:Overexpression of migfilin significantly enhanced cisplatin-induced apoptosis in Hs683, H4, and U-87 MG cells, whereas downregulation of migfilin expression inhibited the chemosensitivity of these cell lines. The N-terminal region of migfilin alone was able to enhance the cisplatin-induced apoptosis. However, despite the existence of the N-terminal region, mutants of migfilin with any one of three LIM domains deleted led to a function loss. Furthermore, apoptotic proteins (PARP and caspase-3) and the anti-apoptotic protein Bcl-xL were modulated by the expression level of migfilin in combination with cisplatin. CONCLUSION:The LIM1-3 domains of migfilin play a key role in sensitizing glioma cells to cisplatin-induced apoptosis through regulation of apoptosis-related proteins.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Fan J,Ou YW,Wu CY,Yu CJ,Song YM,Zhan QMdoi
10.1038/aps.2012.123subject
Has Abstractpub_date
2012-10-01 00:00:00pages
1301-10issue
10eissn
1671-4083issn
1745-7254pii
aps2012123journal_volume
33pub_type
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pub_type： 杂志文章,评审
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