Involvement of a guanine nucleotide-exchange protein, ARF-GEP100/BRAG2a, in the apoptotic cell death of monocytic phagocytes

Journal of Leukocyte Biology

Joel Moss²  Akimasa Someya¹  Isao Nagaoka¹ 

[1] Department of Host Defense and Biochemical Research, Juntendo University School of Medicine, Tokyo, Japan; and Department of Host Defense and Biochemical Research, Juntendo University School of Medicine, Tokyo, Japan; and Department of Host Defense and Biochemical Research, Juntendo University School of Medicine, Tokyo, Japan; and;Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland

关键词: apoptosis;    GEF;    Sec7 domain;    macrophages;    siRNA;   

DOI  :  10.1189/jlb.0106059

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

We previous identified adenosine 5′-diphosphate-ribosylation factor (ARF)-guanine nucleotide-exchange protein, 100 kDa (GEP100), as a novel GEP with a molecular size of ∼100 kDa, which preferentially activates ARF6. In this study, we examined the effect of ARF-GEP100 on monocytic cell apoptosis. Overexpression of ARF-GEP100 in PMA-differentiated human monocyte-macrophage-like U937 cells and mouse macrophage RAW264.7 cells induced apoptotic cell death, which was detected by morphological changes (chromatin condensation, nucleus fragmentation, and shrinking of cytoplasm), annexin V-staining, and TUNEL assay. It is interesting that a mutant lacking the Sec7 domain, which is responsible for ARF activation, was able to induce apoptosis of the target cells to the level of that of a wild-type ARF-GEP100. Furthermore, ARF-GEP100-silencing experiments indicated that the TNF-α-induced apoptosis was significantly suppressed among ARF-GEP100-depressed cells. These observations apparently suggest that ARF-GEP100 is involved in the induction of apoptosis in monocytic phagocytes, possibly independent of ARF activation.

【 授权许可】

Unknown