Apoptotic DNA Fragmentation May Be a Cooperative Activity between Caspase-activated Deoxyribonuclease and the Poly(ADP-ribose) Polymerase-regulated DNAS1L3, an Endoplasmic Reticulum-localized Endonuclease That Translocates to the Nucleus during Apoptosis

Errami, Youssef; Naura, Amarjit S.; Kim, Hogyoung; Ju, Jihang; Suzuki, Yasuhiro; El-Bahrawy, Ali H.; Ghonim, Mohamed A.; Hemeida, Ramadan A.M.; Mansy, Moselhy S.; Zhang, Jianhua; Xu, Ming; Smulson, Mark E.; Brim, Hassan; Boulares, A. Hamid

doi:10.1074/jbc.m112.423061

Cited by 69 publications

(52 citation statements)

References 35 publications

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“…The Caspase-3 is an important executioner caspases, which is activated by any of the initiator caspases. Active Caspase-3 has variety of functions including activation of a latent cytosolic endonuclease, caspase activated deoxyribonuclease that cleaves genomic DNA into oligonucleosomal fragments (Errami et al, 2013). Our findings correlated with the previous findings in which iron-chelator compounds have been reported for multiple mechanisms in the antitumor activity (Richardson et al, 2009).…”

Section: Discussionsupporting

confidence: 89%

Rice Bran Phytic Acid Induced Apoptosis Through Regulation of Bcl-2/Bax and p53 Genes in HepG2 Human Hepatocellular Carcinoma Cells

Al-Fatlawi

Irshad³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 89%

Rice Bran Phytic Acid Induced Apoptosis Through Regulation of Bcl-2/Bax and p53 Genes in HepG2 Human Hepatocellular Carcinoma Cells

Al-Fatlawi

Irshad³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Taken together, DNase1L3 emerges as an important extracellular NETdegrading nuclease, alongside DNaseI, whereas TREX1, but not DNaseII, is implicated in the intracellular degradation of NETs following internalization of NETs by macrophages. DNase1L3 may also participate in the intracellular degradation of DNA from apoptotic cells (41), whereas DNaseI has been implicated in the disposal of necrotic cells (42), both potential sources of autoantigens. The fact that so many endo-and exonucleases participate in DNA degradation testifies to the importance of avoiding unscheduled immune responses to this ubiquitous self-antigen.…”

Section: Discussionmentioning

confidence: 99%

Intra- and Extracellular Degradation of Neutrophil Extracellular Traps by Macrophages and Dendritic Cells

Lazzaretto

Fadeel

2019

The Journal of Immunology

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Neutrophil extracellular traps (NETs) composed of nuclear DNA associated with histones and granule proteins are involved in the extracellular killing of pathogens. Excessive NET formation has been implicated in several noninfectious pathological conditions. The disposal of NETs is, therefore, important to prevent inadvertent effects resulting from the continued presence of NETs in the extracellular environment. In this study, we investigated the interaction of NETs released by freshly isolated, PMA-stimulated primary human neutrophils with primary human monocyte–derived macrophages or dendritic cells (DCs). NETs were internalized by macrophages, and removal of the protein component prevented engulfment of NETs, whereas complexation with LL-37 restored the uptake of “naked” (protein-free) NETs. NETs were also found to dampen the bacterial LPS-induced maturation of DCs. Cytokine profiling was conducted by using a multiplex array following the interaction of NETs with macrophages or DCs, and NETs alone were found to be noninflammatory, whereas immunomodulatory effects were noted in the presence of LPS with significant upregulation of IL-1β secretion, and a marked suppression of other LPS-induced factors including vascular endothelial growth factor (VEGF) in both cell types. Moreover, macrophage digestion of NETs was dependent on TREX1 (also known as DNaseIII), but not DNaseII, whereas extracellular DNase1L3-mediated degradation of NETs was observed for DCs. Collectively, these findings shed light on the interactions between NETs and phagocytic cells and provide new insights regarding the clearance of NETs, double-edged swords of innate immunity.

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“…In particular, caspase-3 is one of the key mediators of apoptosis and is responsible for the proteolytic cleavage of many key proteins, such as PARP 25,26 . Active caspase-3 and cleaved PARP were found after DI treatment in our study.…”

Section: Discussionmentioning

confidence: 99%

Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro

Zhang

Zhou

et al. 2016

Acta Pharmacol Sin

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Aim:Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms.Methods:Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process.Results:DI inhibited the cell viability of AGS and HGC-27 cells in a dose- and time-dependent manner with IC50 values of 12.0 and 28.8 μmol/L, respectively, at 24 h of treatment. Treatment with DI (10–100 μmol/L) dose-dependently promoted tubulin polymerization, and induced significant G2/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase-dependent apoptosis in AGS and HGC-27 cells.Conclusion:DI induces G2/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy.

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Apoptotic DNA Fragmentation May Be a Cooperative Activity between Caspase-activated Deoxyribonuclease and the Poly(ADP-ribose) Polymerase-regulated DNAS1L3, an Endoplasmic Reticulum-localized Endonuclease That Translocates to the Nucleus during Apoptosis

Cited by 69 publications

References 35 publications

Rice Bran Phytic Acid Induced Apoptosis Through Regulation of Bcl-2/Bax and p53 Genes in HepG2 Human Hepatocellular Carcinoma Cells

Rice Bran Phytic Acid Induced Apoptosis Through Regulation of Bcl-2/Bax and p53 Genes in HepG2 Human Hepatocellular Carcinoma Cells

Intra- and Extracellular Degradation of Neutrophil Extracellular Traps by Macrophages and Dendritic Cells

Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro

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