Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10770664 | Biochemical and Biophysical Research Communications | 2005 | 12 Pages |
Abstract
We demonstrate how co-treatment of low-dose staurosporine (STS) and TGF-β1, which alone have little effect on cell death, markedly induces apoptosis in Mv1Lu mink lung epithelial cells, but not in its clonal variant R1B cells lacking functional TGF-β signaling. This process was associated with mitochondria-dependent apoptosis and the enhanced TGF-β/Smad signaling in Mv1Lu cells. When R1B cells were infected with adenovirus carrying wild-type ALK5, a functional TGF-β type I receptor gene, the apoptotic cell death was significantly restored in these cells following co-treatment of low-dose STS and TGF-β1. Treatment of Mv1Lu cells with both low-dose STS and TGF-β1 decreased the activity of phospho-Akt, which is involved in cell survival signal. In addition, pre-treatments of PI3 kinase inhibitors, LY294002 and wortmannin, further increased the apoptosis of MvlLu cells induced by co-treatment of low-dose STS and TGF-β1. And overexpression of constitutively active Akt (myr-Akt) using adenoviral expression system inhibited the apoptotic cell death of Mv1Lu cells by about 50% upon co-treatment of low-dose STS and TGF-β1. These results suggest that co-treatment of low-dose STS and TGF-β1 induces apoptosis of mink lung epithelial cells by enhancing TGF-β signaling and in part suppressing cytoprotective signaling.
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Authors
Eun Mi Ju, Kyung-Chul Choi, Seung-Hee Hong, Chang-Hun Lee, Byung-Chul Kim, Seong-Jin Kim, In-Hoo Kim, Seok Hee Park,