Activation of the abundant nuclear factor poly(ADP-ribose) polymerase-1 by
            <i>Helicobacter pylori</i>

Nossa, Carlos W.; Jain, Prashant; Tamilselvam, Batcha; Gupta, Vijay; Chen, Lin Feng; Schreiber, Valérie; Desnoyers, Serge; Blanke, Steven R.

doi:10.1073/pnas.0906753106

Cited by 25 publications

(28 citation statements)

References 38 publications

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“…Chen et al (49) previously demonstrated that incubating BGC-823 gastric cancer cells with H. pylori extract induced a breakdown of caspase-1 and caspase-3, but not of PARP. Nossa et al (50) subsequently demonstrated that PARP-1 became activated in H. pylori infected gastric epithelial cells. Notably, the present study similarly demonstrated that PARP-1 expression levels were significantly increased in H. pylori infected gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Liu

Zhao

et al. 2016

Oncology Letters

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Poly (adenosine diphosphate-ribose) polymerase 1 (PARP-1) was previously demonstrated to be overexpressed in numerous malignant tumors and associated with invasiveness and poor prognosis. However, the expression of the PARP-1 protein in gastric cancer and its association with clinical outcomes requires further investigation. In the present study, the expression of PARP-1 in 564 gastric cancer tissues and 335 tumor-adjacent control tissues is investigated, using tissue microarray-based immunohistochemistry. PARP-1 expression levels were demonstrated to be significantly higher in gastric cancer tissue samples, as compared with control tissue samples. In gastric cancer, high PARP-1 expression levels were significantly associated with Helicobacter pylori (H. pylori) infection (P=0.032), decreased differentiation (P<0.001), increased depth of invasion (P=0.037), presence of lymphatic invasion (P<0.001), presence of lymph node metastasis (P<0.001), and advanced tumor-node-metastasis (TNM) stage (P=0.015). High PARP-1 expression levels were associated with a significantly shorter overall survival rate (P<0.001) and disease-free survival rate (P=0.001) in patients with gastric cancer, particularly a subset of patients with H. pylori infection or an advanced TNM stage. In addition, univariate analysis indicated that PARP-1 high expression levels were significantly associated with a poor prognosis in gastric cancer. These results suggest that PARP-1 expression may be involved in the progression and prognosis of gastric cancer, particularly H. pylori-positive or advanced-stage gastric cancer.

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Section: Discussionmentioning

confidence: 99%

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Liu

Zhao

et al. 2016

Oncology Letters

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“…H. pylori ) cancers remains to be evaluated clinically. Few studies have demonstrated suppression of the inflammatory response by PARP inhibitors in mice infected with H. pylori (Nossa et al , 2009) and prevention of the formation of Helicobacter -induced precancerous conditions in mice deficient of anti-inflammatory cytokine. PARP-1 sits at the center of the game not only to assist in repair of RONS-induced DNA lesions, but it also can contribute to further damage by promoting inflammation.…”

Section: Interplay Between Infection-induced Inflammation and Dna Repairmentioning

confidence: 99%

Interplay between DNA repair and inflammation, and the link to cancer

Kidane¹,

Chae

Czochor³

et al. 2014

Critical Reviews in Biochemistry and Molecular Biology

134

114

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DNA damage and repair are linked to cancer. DNA damage that is induced endogenously or from exogenous sources has the potential to result in mutations and genomic instability if not properly repaired, eventually leading to cancer. Inflammation is also linked to cancer. Reactive oxygen and nitrogen species (RONs) produced by inflammatory cells at sites of infection can induce DNA damage. RONs can also amplify inflammatory responses, leading to increased DNA damage. Here, we focus on the links between DNA damage, repair, and inflammation, as they relate to cancer. We examine the interplay between chronic inflammation, DNA damage and repair and review recent findings in this rapidly emerging field, including the links between DNA damage and the innate immune system, and the roles of inflammation in altering the microbiome, which subsequently leads to the induction of DNA damage in the colon. Mouse models of defective DNA repair and inflammatory control are extensively reviewed, including treatment of mouse models with pathogens, which leads to DNA damage. The roles of microRNAs in regulating inflammation and DNA repair are discussed. Importantly, DNA repair and inflammation are linked in many important ways, and in some cases balance each other to maintain homeostasis. The failure to repair DNA damage or to control inflammatory responses has the potential to lead to cancer.

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“…To accomplish this simplification, researchers have previously introduced macromolecules into cells by many different methods, including viral transduction 10 , microinjection 11 , scrape loading 12,13 , cell fusion with chemically induced microinjection 14 , proprietary protein “transfection” reagents 15 , calcium phosphate precipitations 16 , and electroporation 17-20 . The introduced molecules range from nucleic acids including DNA, RNA, & RNAi species to proteins, cell-impermeable dyes, and antibodies for intracellular targets 21,22 .…”

Section: Introductionmentioning

confidence: 99%

Electroporation of Functional Bacterial Effectors into Mammalian Cells

Sontag

Mihai

Orr

et al. 2015

JoVE

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The study of protein interactions in the context of living cells can generate critical information about localization, dynamics, and interacting partners. This information is particularly valuable in the context of host-pathogen interactions. Many pathogen proteins function within host cells in a variety of way such as, enabling evasion of the host immune system and survival within the intracellular environment. To study these pathogen-protein host-cell interactions, several approaches are commonly used, including: in vivo infection with a strain expressing a tagged or mutant protein, or introduction of pathogen genes via transfection or transduction. Each of these approaches has advantages and disadvantages. We sought a means to directly introduce exogenous proteins into cells. Electroporation is commonly used to introduce nucleic acids into cells, but has been more rarely applied to proteins although the biophysical basis is exactly the same. A standard electroporator was used to introduce affinity-tagged bacterial effectors into mammalian cells. Human epithelial and mouse macrophage cells were cultured by traditional methods, detached, and placed in 0.4 cm gap electroporation cuvettes with an exogenous bacterial pathogen protein of interest (e.g. Salmonella Typhimurium GtgE). After electroporation (0.3 kV) and a short (4 hr) recovery period, intracellular protein was verified by fluorescently labeling the protein via its affinity tag and examining spatial and temporal distribution by confocal microscopy. The electroporated protein was also shown to be functional inside the cell and capable of correct subcellular trafficking and protein-protein interaction. While the exogenous proteins tended to accumulate on the surface of the cells, the electroporated samples had large increases in intracellular effector concentration relative to incubation alone. The protocol is simple and fast enough to be done in a parallel fashion, allowing for high-throughput characterization of pathogen proteins in host cells including subcellular targeting and function of virulence proteins.

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Activation of the abundant nuclear factor poly(ADP-ribose) polymerase-1 by Helicobacter pylori

Cited by 25 publications

References 38 publications

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Interplay between DNA repair and inflammation, and the link to cancer

Electroporation of Functional Bacterial Effectors into Mammalian Cells

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