Interleukin 3 protects murine bone marrow cells from apoptosis induced by DNA damaging agents

Article (PDF Available)inJournal of Experimental Medicine 176(4):1043-51 · November 1992with12 Reads
Source: PubMed
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.

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Available from: Jacqueline Marvel
    • "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.
    Full-text · Article · Apr 2014
    • "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 [15] . 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 [18]. "
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    • "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. "
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