Overexpression of tissue factor pathway inhibitor in CHO-K1 cells results in increased activation of NF-κB and apoptosis mediated by a caspase-3 independent pathway
Skretting, G; Iversen, N; Myklebust, CF; Dahm, AE; Sandset, PM
HERO ID
1454699
Reference Type
Journal Article
Year
2012
Language
English
PMID
| HERO ID | 1454699 |
|---|---|
| In Press | No |
| Year | 2012 |
| Title | Overexpression of tissue factor pathway inhibitor in CHO-K1 cells results in increased activation of NF-κB and apoptosis mediated by a caspase-3 independent pathway |
| Authors | Skretting, G; Iversen, N; Myklebust, CF; Dahm, AE; Sandset, PM |
| Journal | Molecular Biology Reports |
| Volume | 39 |
| Issue | 12 |
| Page Numbers | 10089-10096 |
| Abstract | There is now circumstantial evidence that tissue factor pathway inhibitor (TFPI) is not only a major anticoagulant, but also has proapoptotic properties. The current study was designed to address the role of TFPI on signalling pathways and apoptosis. The non-TFPI expressing cell line CHO-K1 was stably transfected with pcDNA3.1/V5-His-TOPO-TFPI and control cells were established by transfecting the CHO-K1 cells with pcDNA3.1/V5-His-TOPO. Sodium butyrate (NaBut) has been shown to induce the expression of recombinant proteins. Here we have used NaBut to increase the expression of TFPI as assessed by qRT-PCR and ELISA. Compared to the control cells, TFPI induced apoptosis in a concentration dependent manner as measured by a cell death detection assay. Independent of caspase-3 activation an increased cleavage of PARP was detected in the TFPI expressing cells. This was accompanied by downregulation of Bcl-XL, elevated levels of Bax, and increased translocation of the apoptosis initiating factor. Increased DNA binding activity of NF-κB was revealed by electrophoretic mobility shift assay when the TFPI level was elevated by NaBut together with an increased translocation of the NF-κB subunit p65. The results indicate that TFPI affected the apoptotic activity through a process independent of caspase-3, and was also able to increase the activation of the NF- κB pathway. |
| Doi | 10.1007/s11033-012-1882-7 |
| Pmid | 22932941 |
| Wosid | WOS:000310586700012 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Tissue factor pathway inhibitor; CHO-K1 cells; Apoptosis; NF-kappa B; Anti-cancer; Na-butyrate |