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

Abstract

SummaryMurine bone marrow-derived cells, dependent on interleukin 3 (I1.3) 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 I1.-3. In contrast, when cultured in the presence of I1.3, 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 I1-3 is not required during the initial events of DNA damage or its repair. In the absence of I1-3, cells still complete the repair of DNA breaks within 15 min, and continue to cycle for 5 h. At this time, I1-3 is necessary to prevent the accelerated onset of DNA cleavage from a G2 arrest point.

Ultrarapid caspase-3 dependent apoptosis induction by serine/threonine phosphatase inhibitors

“…Examples hereof are the Fas/Apo-1/CD95-system 47 (and references therein), glucocorticoid-induced thymocyte apoptosis, 48 growth factor (e.g. IL-3) withdrawal, 49 and cAMP-induced apoptosis of the presently studied IPC-81 leukemia cells. 50 On the basis of the results presented, it seems reasonable to suggest that phosphatase inhibitors have evolved as rapidly lethal toxins by acquiring ability to short-cut normal apoptotic pathways, presumably acting close to the execution machinery.…”

Bcl-2 and the regulation of programmed cell death

“…Though few mechanistic details are known at this point, these data have suggested that bcl-2 blocks a final common pathway leading to apoptotic cell death. The participants in this pathway remain unknown, but the observation that bcl-2 blocks apoptosis induced by multiple chemotherapeutic drugs as well as 3'-irradiation provides some clues that may help to provide at least a partial explanation Reed, 1992, 1993;Lotem and Sachs, 1993;Fanidi et al, 1992;Collins et al, 1992; J. C. Reed, unpublished observations). For example, 3,-irradiation and the wide variety of drugs to which Bcl-2 confers resistance have diverse mechanisms of action, but all induce DNA damage either directly or indirectly.…”

NBS1 is required for macrophage homeostasis and functional activity in mice

“…28,29 To address this, we first examined the expression of Nbs1 in macrophages to determine whether it was modulated by different stimulatory agents. We obtained murine BM and differentiated it in vitro to BMDMs.…”