S-nitrosation on zinc finger motif of PARP-1 as a mechanism of DNA repair inhibition by arsenite

Zhou, Xixi; Cooper, Karen L.; Huestis, Juliana; Xu, Huan; Burchiel, Scott W.; Hudson, Laurie G.; Liu, Ke Jian

doi:10.18632/oncotarget.12613

Cited by 26 publications

(19 citation statements)

References 35 publications

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“…Arsenite enhanced UVR- induced oxidative DNA damage by inhibiting the activity and function of PARP-1 (Sun et al, 2014; Zhou et al, 2016). The present study demonstrates that arsenite displaces zinc and inhibits chromatin association of the NER protein XPA in a similar manner to that of PARP-1.…”

Section: Discussionmentioning

confidence: 99%

Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue

Ding

Zhou

Cooper

et al. 2017

Toxicology and Applied Pharmacology

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Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)- induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA). In this study, we investigated the difference in response to arsenite exposure between XPA and PARP-1, and the differential effectiveness of zinc supplementation in restoring protein DNA binding and DNA damage repair. Arsenite targeted both XPA and PARP-1 in human keratinocytes, resulting in zinc loss from each protein and a pronounced decrease in XPA and PARP-1 binding to chromatin as demonstrated by Chip-on-Western assays. Zinc effectively restored DNA binding of PARP-1 and XPA to chromatin when zinc concentrations were equal to those of arsenite. In contrast, zinc was more effective in rescuing arsenite-augmented direct UVR- induced DNA damage than oxidative DNA damage. Taken together, our findings indicate that arsenite interferes with PARP-1 and XPA binding to chromatin, and that zinc supplementation fully restores DNA binding activity to both proteins in the cellular context. Interestingly, rescue of arsenite- inhibited DNA damage repair by supplemental zinc was more sensitive for DNA damage repaired by the XPA-associated NER pathway than for the PARP-1-dependent BER pathway. This study expands our understanding of arsenite’s role in DNA repair inhibition and co-carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue

Ding

Zhou

Cooper

et al. 2017

Toxicology and Applied Pharmacology

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“…Both zinc deficiency and arsenic exposure modulate oxidative stress, inflammation, DNA repair and metabolism ( 12 , 21 , 33 , 48 – 51 ). Correspondingly, our study finds that marginal zinc deficiency and arsenic exposure both independently increased DNA damage and decreased plasma zinc.…”

Section: Discussionmentioning

confidence: 99%

Marginal Zinc Deficiency and Environmentally Relevant Concentrations of Arsenic Elicit Combined Effects on the Gut Microbiome

Gaulke

Rolshoven

Wong

et al. 2018

mSphere

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Xenobiotic compounds, such as arsenic, have the potential to alter the composition and functioning of the gut microbiome. The gut microbiome may also interact with these compounds to mediate their impact on the host. However, little is known about how dietary variation may reshape how the microbiome responds to xenobiotic exposures or how these modified responses may in turn impact host physiology. Here, we investigated the combinatorial effects of marginal zinc deficiency and physiologically relevant concentrations of arsenic on the microbiome. Both zinc deficiency and arsenic exposure were individually associated with altered microbial diversity and when combined elicited synergistic effects. Microbial abundance also covaried with host physiological changes, indicating that the microbiome may contribute to or be influenced by these pathologies. Collectively, this work demonstrates that dietary zinc intake influences the sensitivity of the microbiome to subsequent arsenic exposure.

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“…Excess NO could cause damage to cells or tissues through targeting DNA, mitochondria, cell membranes and proteins [3,22,23]. Growing body of evidence indicated that NO and NOS-derived NO production are positively correlated with apoptosis [4].…”

Section: Discussionmentioning

confidence: 99%

Effects of Ghrelin on iNOS-Derived NO Promoted LPS-Induced Pulmonary Alveolar Epithelial A549 Cells Apoptosis

Zeng

Huang

Zheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: In the process of abnormal apoptosis of pulmonary alveolar type II epithelial A549 cells in acute respiratory distress syndrome (ARDS), inducible nitric oxide synthase (iNOS) activity in the lung, nitric oxide (NO) production, and the level of protein S-nitrosylation were increased. However, the role of excessive NO production in sepsis-induced ARDS is controversial. Additionally, ghrelin is a growth hormone that exerts an inhibitory role in cell apoptosis. We examined the effect of NO and S-nitrosylation on apoptosis of A549 cells induced by Lipopolysaccharide (LPS) and molecular mechanism underlying the anti-apoptotic effect of ghrelin in this process. Methods: Flow cytometry and qPCR were used to detect lentiviral infection efficiency and iNOS gene level, respectively. Extracellular and intracellular NO levels were observed by Griess assay kit and DAF-FM DA. Mitochondrial transmembrane potential, apoptosis rate and SNO levels were determined by flow cytometry, Biotin-Switch method and immunofluoresence staining. The expression of iNOS, apoptotic proteins and JNK were assessed by immunoblot analysis. Results: The results showed about two times increase in iNOS expression and intracellular NO levels response to LPS exposure at 24 hours (P< 0.05), while not in extracellular NO levels. NO donors, S-nitroso-N-acetylpenicillamine (SNAP) significantly raised (36.7%, P< 0.05; 38.4%, P< 0.05; 41.8%, P< 0.05) extracellular NO levels without influencing the intracellular NO levels. LPS increased the apoptosis rate (42.4%±2.6% vs 2.8%±1%, P< 0.05) of A549 accompanied by increased Bax levels and decreased Bcl-2 levels through activating JNK signaling, which was reversed when we diminished the iNOS expression in A549 cells using lentiviral vectors encoding iNOS shRNA in the presence of LPS (24.8%±3.8% vs 42.4%±2.6%, P< 0.05). However, the apoptosis rate was increased when SNAP was added (38.8%±1.3% vs 24.8%±3.8%, P< 0.05). Furthermore, we investigated whether ghrelin exert a protective role against LPS-induced apoptosis and the potential mechanism involved in. Ghrelin alone appeared to decrease iNOS expression (32.3%, P< 0.05; 42.3%, P< 0.05), which showed no signifiant difference between LPS+ghrelin group and LPS group. However, this study showed that ghrelin decreased the intracellular NO production (38.9%, P< 0.05), protein S-nitrosylation levels (33.5%, P< 0.05), Bax protein expression (70.2%, P< 0.05), whereas increasing Bcl-2 protein expression (14.1%, P< 0.05) and mitochondrial transmembrane potential (∆ΨM) (20.7%, P< 0.05) in the presence of LPS. Conclusion: The data suggested that NO derived from iNOS induced by LPS stimulation exerts an important role in promoting apoptosis of A549 cells, and ghrelin abolished intracellular NO production and protein S-nitrosylation levels, abrogating the apoptosis of A549 cells partly through inhibiting mitochondrial-dependent pathways.

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S-nitrosation on zinc finger motif of PARP-1 as a mechanism of DNA repair inhibition by arsenite

Cited by 26 publications

References 35 publications

Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue

Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue

Marginal Zinc Deficiency and Environmentally Relevant Concentrations of Arsenic Elicit Combined Effects on the Gut Microbiome

Effects of Ghrelin on iNOS-Derived NO Promoted LPS-Induced Pulmonary Alveolar Epithelial A549 Cells Apoptosis

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