Zoledronic Acid Activates the DNA S-Phase Checkpoint and Induces Osteosarcoma Cell Death Characterized by Apoptosis-Inducing Factor and Endonuclease-G Translocation Independently of p53 and Retinoblastoma Status

2006 ◽  
Vol 71 (1) ◽  
pp. 333-343 ◽  
Author(s):  
B. Ory ◽  
F. Blanchard ◽  
S. Battaglia ◽  
F. Gouin ◽  
F. Rédini ◽  
...  
Keyword(s):  
Cell Death ◽  
Zoledronic Acid ◽  
S Phase ◽  
Osteosarcoma Cell ◽  
Endonuclease G ◽  
Apoptosis Inducing Factor ◽  
S Phase Checkpoint

scholarly journals BUB1 mediation of caspase-independent mitotic death determines cell fate

2007 ◽  
Vol 178 (2) ◽  
pp. 283-296 ◽  
Author(s):  
Yohei Niikura ◽  
Amruta Dixit ◽  
Ray Scott ◽  
Guy Perkins ◽  
Katsumi Kitagawa
Keyword(s):  
Cell Death ◽  
Cell Fate ◽  
Cell Lines ◽  
Chromosome Instability ◽  
Spindle Checkpoint ◽  
Mitotic Cell ◽  
Endonuclease G ◽  
Colon Tumors ◽  
Mitotic Death ◽  
Apoptosis Inducing Factor

The spindle checkpoint that monitors kinetochore–microtubule attachment has been implicated in tumorigenesis; however, the relation between the spindle checkpoint and cell death remains obscure. In BUB1-deficient (but not MAD2-deficient) cells, conditions that activate the spindle checkpoint (i.e., cold shock or treatment with nocodazole, paclitaxel, or 17-AAG) induced DNA fragmentation during early mitosis. This mitotic cell death was independent of caspase activation; therefore, we named it caspase-independent mitotic death (CIMD). CIMD depends on p73, a homologue of p53, but not on p53. CIMD also depends on apoptosis-inducing factor and endonuclease G, which are effectors of caspase-independent cell death. Treatment with nocodazole, paclitaxel, or 17-AAG induced CIMD in cell lines derived from colon tumors with chromosome instability, but not in cells from colon tumors with microsatellite instability. This result was due to low BUB1 expression in the former cell lines. When BUB1 is completely depleted, aneuploidy rather than CIMD occurs. These results suggest that cells prone to substantial chromosome missegregation might be eliminated via CIMD.

scholarly journals Endonuclease G does not play an obligatory role in poly(ADP-ribose) polymerase-dependent cell death after transient focal cerebral ischemia

2010 ◽  
Vol 299 (1) ◽  
pp. R215-R221 ◽  
Author(s):  
Zhenfeng Xu ◽  
Jian Zhang ◽  
Karen K. David ◽  
Zeng-Jin Yang ◽  
Xiaoling Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Nuclear Translocation ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Wild Type ◽  
Endonuclease G ◽  
Transient Focal Cerebral Ischemia ◽  
Apoptosis Inducing Factor

Activation of poly(ADP-ribose) polymerase (PARP) and subsequent translocation of apoptosis-inducing factor contribute to caspase-independent neuronal injury from N-methyl-d-aspartate, oxygen-glucose deprivation, and ischemic stroke. Some studies have implicated endonuclease G in the DNA fragmentation associated with caspase-independent cell death. Here, we compared wild-type and endonuclease G null mice to investigate whether endonuclease G plays a role in the PARP-dependent injury that results from transient focal cerebral ischemia. Latex casts did not reveal differences in the cerebral arterial distribution territory or posterior communicating arterial diameter, and the decrease in laser-Doppler flux during middle cerebral artery occlusion was similar in wild-type and endonuclease G null mice. After 90 min of occlusion and 1 day of reperfusion, similar degrees of nuclear translocation of apoptosis-inducing factor and DNA degradation were evident in male wild-type and null mice. At 3 days of reperfusion, infarct volume and neurological deficit scores were not different between male wild-type and endonuclease G null mice or between female wild-type and endonuclease G null mice. These data demonstrate that endonuclease G is not required for the pathogenesis of transient focal ischemia in either male or female mice. Treatment with a PARP inhibitor decreased infarct volume and deficit scores equivalently in male wild-type and endonuclease G null mice, indicating that the injury in endonuclease G null mice remains dependent on PARP. Thus endonuclease G is not obligatory for executing PARP-dependent injury during ischemic stroke.

Zoledronic acid induces osteosarcoma cell death by aif translocation and cell cycle arrest in S and G2/M phases

Bone ◽  
2006 ◽  
Vol 38 (3) ◽  
pp. 59
Author(s):  
B. Ory ◽  
F. Blanchard ◽  
S. Couillaud ◽  
F. Gouin ◽  
F. Rédini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Zoledronic Acid ◽  
Cell Cycle Arrest ◽  
Osteosarcoma Cell ◽  
Cycle Arrest

scholarly journals MGL induces nuclear translocation of EndoG and AIF in caspase-independent T cell death

2015 ◽  
Vol 20 (5) ◽  
Author(s):  
Qingpan Bu ◽  
Jianhui Wang ◽  
Yi Zheng ◽  
Yingying Zou ◽  
Min Wei
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Cell Apoptosis ◽  
Nuclear Translocation ◽  
Endonuclease G ◽  
T Cell Apoptosis ◽  
Lectin Family ◽  
Apoptosis Inducing Factor

AbstractMacrophage galactose-type lectin (MGL) participates in the regulation of T cell apoptosis, but the exact death pathway remains unclear. Here, we demonstrated that MGL-induced T cell death occurs in a caspaseindependent manner. Furthermore, MGL treatment triggers the translocation of endonuclease G (EndoG) and apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. Because galectin-1 (Gal-1) can also initiate similar mitochondrial events, we speculate that this death pathway may be widely used by the lectin family.

scholarly journals Drp1 Mediates Caspase-Independent Type III Cell Death in Normal and Leukemic Cells

2007 ◽  
Vol 27 (20) ◽  
pp. 7073-7088 ◽  
Author(s):  
Marlène Bras ◽  
Victor J. Yuste ◽  
Gaël Roué ◽  
Sandrine Barbier ◽  
Patricia Sancho ◽  
...  
Keyword(s):  
Cell Death ◽  
Serine Proteases ◽  
Reactive Oxygen Species Generation ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Mrna Levels ◽  
Endonuclease G ◽  
Type Iii ◽  
Transport Chain ◽  
Apoptosis Inducing Factor

ABSTRACT Ligation of CD47 triggers caspase-independent programmed cell death (PCD) in normal and leukemic cells. Here, we characterize the morphological and biochemical features of this type of death and show that it displays the hallmarks of type III PCD. A molecular and biochemical approach has led us to identify a key mediator of this type of death, dynamin-related protein 1 (Drp1). CD47 ligation induces Drp1 translocation from cytosol to mitochondria, a process controlled by chymotrypsin-like serine proteases. Once in mitochondria, Drp1 provokes an impairment of the mitochondrial electron transport chain, which results in dissipation of mitochondrial transmembrane potential, reactive oxygen species generation, and a drop in ATP levels. Surprisingly, neither the activation of the most representative proapoptotic members of the Bcl-2 family, such as Bax or Bak, nor the release of apoptogenic proteins AIF (apoptosis-inducing factor), cytochrome c, endonuclease G (EndoG), Omi/HtrA2, or Smac/DIABLO from mitochondria to cytosol is observed. Responsiveness of cells to CD47 ligation increases following Drp1 overexpression, while Drp1 downregulation confers resistance to CD47-mediated death. Importantly, in B-cell chronic lymphocytic leukemia cells, mRNA levels of Drp1 strongly correlate with death sensitivity. Thus, this previously unknown mechanism controlling caspase-independent type III PCD may provide the basis for novel therapeutic approaches to overcome apoptotic avoidance in malignant cells.

scholarly journals Apoptosis inducing factor and mitochondrial NADH dehydrogenases: redox-controlled gear boxes to switch between mitochondrial biogenesis and cell death

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Johannes M. Herrmann ◽  
Jan Riemer
Keyword(s):  
Cell Death ◽  
Complex I ◽  
Electron Transfer Reaction ◽  
Apoptotic Protein ◽  
Transport Chain ◽  
Metabolic Conditions ◽  
Nadh Dehydrogenases ◽  
The One ◽  
Apoptosis Inducing Factor ◽  
Redox Switches

AbstractThe mitochondrial complex I serves as entry point for NADH into the electron transport chain. In animals, fungi and plants, additional NADH dehydrogenases carry out the same electron transfer reaction, however they do not pump protons. The apoptosis inducing factor (AIF, AIFM1 in humans) is a famous member of this group as it was the first pro-apoptotic protein identified that can induce caspase-independent cell death. Recent studies on AIFM1 and the NADH dehydrogenase Nde1 of baker’s yeast revealed two independent and experimentally separable activities of this class of enzymes: On the one hand, these proteins promote the functionality of mitochondrial respiration in different ways: They channel electrons into the respiratory chain and, at least in animals, promote the import of Mia40 (named MIA40 or CHCHD4 in humans) and the assembly of complex I. On the other hand, they can give rise to pro-apoptotic fragments that are released from the mitochondria to trigger cell death. Here we propose that AIFM1 and Nde1 serve as conserved redox switches which measure metabolic conditions on the mitochondrial surface and translate it into a binary life/death decision. This function is conserved among eukaryotic cells and apparently used to purge metabolically compromised cells from populations.

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