Negative Feedback Loop in the Bim–Caspase-3 Axis Regulating Apoptosis and Activity of Osteoclasts

Wakeyama, Hidetoshi; Akiyama, Tsuyoshi; Takahashi, K.; Amano, Hitoshi; Kadono, Yuho; Nakamura, Masaki; Oshima, Yasushi; Itabe, Hiroyuki; Nakayama, Keiichi I.; Nakayama, Keiko; Nakamura, Kozo; Tanaka, Sakae

doi:10.1359/jbmr.070619

Cited by 36 publications

(24 citation statements)

References 44 publications

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“…4). The initial high levels of Bim proteins (especially BimEL) may mediate the apoptosis-inducing effect of anisomycin, while caspase-3-dependent degradation of Bim proteins may function as a negative feed-back mechanism [39]. The activation pattern of JNK is consistent with its role in the initiation of intrinsic apoptotic pathway.…”

Section: Discussionmentioning

confidence: 63%

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Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells

et al. 2017

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The bacterial antibiotic anisomycin is known to induce apoptosis by activating several mitogen-activated protein kinases and by inhibiting protein synthesis. In this study, the influence of p53 protein on the apoptosis-inducing effect of anisomycin was investigated. The effect of protein synthesis-inhibiting concentration of anisomycin on apoptotic events was analyzed using Western blot, DNA fragmentation, and cell viability assays in wild-type PC12 and in mutant p53 protein expressing p143p53PC12 cells. Anisomycin stimulated the main apoptotic pathways in both cell lines, but p143p53PC12 cells showed lower sensitivity to the drug than their wild-type counterparts. Anisomycin caused the activation of the main stress kinases, phosphorylation of the p53 protein and the eukaryotic initiation factor eIF2α, proteolytic cleavage of protein kinase R, Bid, caspase-9 and -3. Furthermore, anisomycin treatment led to the activation of TRAIL and caspase-8, two proteins involved in the extrinsic apoptotic pathway. All these changes were stronger and more sustained in wtPC12 cells. In the presence of the dominant inhibitory p53 protein, p53- dependent genes involved in the regulation of apoptosis may be less transcribed and this can lead to the decrease of apoptotic processes in p143p53PC12 cells.

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Section: Discussionmentioning

confidence: 63%

“…We did not examine the phosphorylation status of the Bim isoforms in this study, but we found, somewhat unexpectedly, a decreased level of Bim protein in both cell lines. It may represent a negative feed-back mechanism in the regulation of the intrinsic pathway of apoptosis [39].…”

Section: Mapks Are Differentially Affected By Anisomycin Treatment Inmentioning

confidence: 99%

Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells

et al. 2017

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“…Mcl-1, Bim, and Bcl-xL can be degraded by active caspases in dying cells, [34][35][36][37][38][39] which might also contribute to the observed decrease of these 3 proteins (supplemental Figure 3). …”

Section: -33mentioning

confidence: 99%

Inhibition of Mcl-1 with the pan–Bcl-2 family inhibitor (–)BI97D6 overcomes ABT-737 resistance in acute myeloid leukemia

Pan

Ruvolo

Wei

et al. 2015

Blood

122

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“…Bim may be degraded by caspase-3 as a negative feedback mechanism in osteoclasts (46). The caspase-cleaved form of Lyn exerts a negative feedback on imatinib-mediated chronic myelogenous leukemia cell apoptosis that is entirely dependent on its kinase activity (47).…”

Section: Tdp-43 Cleavage Leads To the Attenuation Of Tdp-43-inducedmentioning

confidence: 99%

TDP-43-induced Death Is Associated with Altered Regulation of BIM and Bcl-xL and Attenuated by Caspase-mediated TDP-43 Cleavage

Suzuki

Lee

Matsuoka

2011

Journal of Biological Chemistry

102

110

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FTLD-U is the most common variant of FTLD. FTLD, a heterogeneous syndrome characterized by progressive dementia, is caused by degeneration of the frontal and anterior temporal lobes, and is a leading cause of dementia in patients presenting before the age of 65 years (5). The pathogenesis of FTLD remains unknown. ALS is the most common motor neuron disease, characterized by progressive loss of motor neurons (6, 7). The pathogenesis of ALS remains undetermined although various hypotheses have been proposed: e.g. misfolded protein aggregates, mitochondrial dysfunction, glutamate toxicity, oxidative stress, disturbance of intracellular trafficking, and ER stress (8). About 10% of ALS cases occur in a genetically inherited manner.Post-translational modifications of TDP-43 including truncation, hyperphosphorylation, and ubiquitination are assumed to be linked to abnormal aggregation (1, 2). In particular, C-terminal fragments (CTFs) of TDP-43 are prone to form cytoplasmic aggregates (9 -11). Although it is apparent that cytoplasmic aggregates of TDP-43 are closely related to the pathogenesis of FTLD-U and ALS, it remains unknown how CTFs are generated and whether the aggregate formation of TDP-43 is a cause or a result of neuronal toxicity.Caspase activation has been observed in motor neurons of ALS (12-15) and neurons in FTLD patients (16). One possible mechanism underlying the generation of CTFs is the cleavage of TDP-43 by activated caspases. In reality, multiple studies have shown that TDP-43 is cleaved in a caspase-dependent manner and the resulting CTFs of TDP-43 are constituents in the inclusion bodies (17)(18)(19).Some clinical studies have suggested that the levels of TDP-43 are up-regulated in motor neurons of sporadic ALS patients, based on the finding that the levels of TDP-43 are up-regulated in cerebrospinal fluids (20)

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Negative Feedback Loop in the Bim–Caspase-3 Axis Regulating Apoptosis and Activity of Osteoclasts

Cited by 36 publications

References 44 publications

Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells

Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells

Inhibition of Mcl-1 with the pan–Bcl-2 family inhibitor (–)BI97D6 overcomes ABT-737 resistance in acute myeloid leukemia

TDP-43-induced Death Is Associated with Altered Regulation of BIM and Bcl-xL and Attenuated by Caspase-mediated TDP-43 Cleavage

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