Murine bone marrow-derived cells, dependent on interleukin 3 (IL-3) for their growth in culture, undergo programmed cell, or apoptosis, upon cytokine withdrawal. Here it is reported that a variety of DNA damaging agents cause a more rapid onset of apoptosis in a factor-dependent cell line, BAF3, deprived of IL-3. In contrast, when cultured in the presence of IL-3, or other growth promoting factors, BAF3 cells are highly resistant to X-irradiation and the cytotoxic drugs etoposide and cisplatin. Overexpression of the bcl2 gene product also protects BAF3 cells from DNA damage. The presence of IL-3 is not required during the initial events of DNA damage or its repair. In the absence of IL-3, cells still complete the repair of DNA breaks within 15 min, and continue to cycle for 5 h. At this time, IL-3 is necessary to prevent the accelerated onset of DNA cleavage from a G2 arrest point.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
"For example, IL-6 has been shown to protect myeloid cells from apoptosis that is induced by a temperature-sensitive mutant of p53 (YonishRouach et al., 1991). Similarly, in BAF-3 cells, IL-3 stimulation has been shown to prevent p53-induced apoptosis but not cell cycle arrest upon c-irradiation (Canman et al., 1995; Collins et al., 1992). Furthermore, constitutively active PI3K or AKT have been shown to slow down the rate of p53-mediated apoptosis (Sabbatini and McCormick, 1999). "
[Show abstract][Hide abstract]ABSTRACT: Glycogen synthase kinase 3 (GSK-3) is involved in various signaling pathways controlling metabolism, differentiation and immunity, as well as cell death and survival. GSK-3 targets transcription factors, regulates the activity of metabolic and signaling enzymes, and controls the half-life of proteins by earmarking them for degradation. GSK-3 is unique in its mode of substrate recognition and the regulation of its kinase activity, which is repressed by pro-survival phosphoinositide 3-kinase (PI3K)-AKT signaling. In turn, GSK-3 exhibits pro-apoptotic functions when the PI3K-AKT pathway is inactive. Nevertheless, as GSK-3 is crucially involved in many signaling pathways, its role in cell death regulation is not uniform, and in some situations it promotes cell survival. In this Commentary, we focus on the various aspects of GSK-3 in the regulation of cell death and survival. We discuss the effects of GSK-3 on the regulation of proteins of the BCL-2 family, through which GSK-3 exhibits pro-apoptotic activity. We also highlight the pro-survival activities of GSK-3, which are observed in the context of nuclear factor κB (NFκB) signaling, and we discuss how GSK-3, by impacting on cell death and survival, might play a role in diseases such as cancer.
"BAF3 cells resisted X-ray-and cytotoxin-induced injury when the culture media was supplemented with IL-3. Treatment with IL-3 exerted no apparent effect on early-stage DNA damage and repair , but played an essential role in preventing the acceleration of DNA fragmentation at the G2 phase block point  . In addition, IL-3 can accelerate G2/M phase arrest and prevent apoptosis of mouse hematopoietic progenitor 32D and human UT7 cell lines in response to etoposide, a type II topoisomerase inhibitor . "
[Show abstract][Hide abstract]ABSTRACT: The previous investigation demonstrated the radioprotective efficacy of peptides isolated from the venom of Buthus Martti Karsch. In this study, the effect of isolated scorpion venom peptide II (SVPII) on irradiated M-NFS-60 cells and mouse bone marrow mononuclear cells (BM-MNCs) was observed. The AlamarBlue cell viability assay, a colony-forming unit (CFU) assay, flow cytometry (FCM), immunofluorescence, and Western blotting were used to evaluate cell proliferation, cell cycle progression, and the expression of the IL-3 receptor (IL-3R) protein in non-irradiated and irradiated cells.
Proliferation of irradiated M-NFS-60 cells was significantly accelerated by SPVII, and this effect was further enhanced by co-application of IL-3. Similarly, SPVII increased the number of BM-MNC CFUs and this proliferative effect was greater in the presence of SVPII plus IL-3. In addition, SPVII significantly altered cell cycle progression; SVPII enhanced the fraction of unirradiated M-NFS-60 cells in S phase and the fraction of irradiated M-NFS-60 cells arrested in G2/M. The expression of IL-3R protein by unirradiated M-NFS-60 cells was enhanced significantly by SVPII, and SVPII-induced IL-3R overexpression was 10-fold greater in irradiated M-NFS-60 cells.
These results indicated the hematopoietic growth factor (HGF)-like effects of SVPII on irradiated cells, possibly mediated by upregulation of IL-3R.
Full-text · Article · Jul 2013 · Cell and Bioscience
"The first two populations were cultured in IL-3 containing media prior to factor withdrawal. As reported previously, removal of IL-3 from control Ba/F3 cells results in loss of cell viability that begins within 24 h after factor withdrawal. (28) Removal of IL-3 from stably transfected cells also resulted in cell death with similar kinetics as control cells. CID withdrawal from CID-selected cells reversed proliferation and resulted in cell death. "
[Show abstract][Hide abstract]ABSTRACT: The main methods for producing genetically engineered cells use viral vectors for which safety issues and manufacturing costs
remain a concern. In addition, selection of desired cells typically relies on the use of cytotoxic drugs with long culture
times. Here, we introduce an efficient non-viral approach combining the Sleeping Beauty (SB) Transposon System with selective proliferation of engineered cells by chemically induced dimerization (CID) of growth factor
receptors. Minicircles carrying a SB transposon cassette containing a reporter transgene and a gene for the F36VFGFR1 fusion protein were delivered to the hematopoietic
cell line Ba/F3. Stably-transduced Ba/F3 cell populations with >98% purity were obtained within 1 week using this positive
selection strategy. Copy number analysis by quantitative PCR (qPCR) revealed that CID-selected cells contain on average higher
copy numbers of transgenes than flow cytometry-selected cells, demonstrating selective advantage for cells with multiple transposon
insertions. A diverse population of cells is present both before and after culture in CID media, although site-specific qPCR
of transposon junctions show that population diversity is significantly reduced after selection due to preferential expansion
of clones with multiple integration events. This non-viral, positive selection approach is an attractive alternative for producing
Full-text · Article · Mar 2012 · Nucleic Acids Research