Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic infection with hepatitis B virus (HBV) is associated with an increased risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Although clonal HBV DNA integrations are detected in nearly all HCCs the role of these integrations in hepatocarcinogenesis is poorly understood. We have used a cloning protocol that allows studying the frequency and the natural history of HBV DNA integrations in cell culture. Southern blot analysis of the genomic DNA of HepG2 2.2.15 subclones, which replicate HBV, enabled us to detect new HBV DNA integrations in approximately 10% of the HepG 2.2.15 subclones over 4 rounds of sequential subcloning, whereas no loss of any preexisting HBV DNA integrations was observed. Treatments of HepG2 cells with H(2)O(2), designed to increase DNA damage, increased the frequency of HBV integrations to approximately 50% of the subclones and treatments designed to inhibit DNA repair, by inhibiting Poly(ADP-ribosyl)ation, also increased the frequency of HBV integration to 50%. These findings suggest that DNA strand breaks induced by oxidative stress during persistent HBV infection in humans may increase HBV DNA integration events, whereas PARP-1 activity may function to limit the occurrence of de novo HBV DNA integrations.
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PMID:Increase in de novo HBV DNA integrations in response to oxidative DNA damage or inhibition of poly(ADP-ribosyl)ation. 1178 79

Chronic infection of the human stomach by Helicobacter pylori is an important risk factor for gastric cancer. H. pylori produces a cache of virulence factors that promote colonization and persistence, which, in turn, contributes to a robust inflammatory response at the host-pathogen interface. Recently, we reported that H. pylori activates the abundant nuclear regulator poly(ADP-ribose) polymerase (PARP)-1, resulting in the production of the catabolite poly(ADP-ribose) (PAR). PARP-1 is emerging as a key player in establishing homeostasis at the host-pathogen interface. In this article, we summarize the discovery of H. pylori-dependent PARP-1 activation, and discuss potential roles for PARP-1 in H. pylori-mediated gastric disease. In light of the remarkable successes that have reported for treating inflammatory disorders and cancers with PARP-1 inhibitors, we discuss the prospects of targeting PARP-1 for treatment of H. pylori-associated gastric disease.
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PMID:Helicobacter pylori activation of PARP-1: usurping a versatile regulator of host cellular health. 2146 18