Increased DNA Damage in Progression Of COPD: A Response By Poly(ADP-Ribose) Polymerase-1

Oit-Wiscombe, Ingrid; Virág, László; Soomets, Ursel; Altraja, Alan

doi:10.1371/journal.pone.0070333

Cited by 16 publications

(14 citation statements)

References 35 publications

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“…We hypothesize that smoke-mediated activation of the parthanatos pathway of programmed cell death produces inflammation that if chronic, results in airway remodeling. Evidence for this is suggested by the finding that in COPD patients increasing PARP-1 activity correlates with disease severity 33 . Thus, smoke-mediated activation of the parthanatos pathway may represent one mechanism directly linking smoke exposure to the chronic inflammation of bronchial epithelia seen in smoking related diseases.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells

Künzi

Holt

2019

Cell Death Discov.

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Tobacco smoke negatively affects human bronchial epithelial (HBE) cells and is directly implicated in the etiology of smoking related respiratory diseases. Smoke exposure causes double-stranded DNA breaks and DNA damage activates PARP-1, the key mediator of the parthanatos pathway of cell death. We hypothesize that smoke exposure activates the parthanatos pathway in HBE cells and represents a cell death mechanism that contributes to smoking related lung diseases. We exposed fully differentiated, primary HBE cells grown at the air liquid interface to cigarette smoke and evaluated them for parthanatos pathway activation. Smoke exposure induced mitochondrial to nuclear translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) within the first three hours characteristic of the parthanatos pathway. Exposing cells to an increasing number of cigarettes revealed that significant activation of the parthanatos pathway occurs after exposure to higher levels of smoke. Use of the specific PARP-1 inhibitor, BMN673, abrogated the effect of smoke induced activation of the parthanatos pathway. Smoke-mediated activation of the parthanatos pathway is increased in HBE cells originating from habitual smokers compared to non-smokers. This suggests that chronic smoke exposure leads to an increase in smoke-mediated activation of the parthanatos pathway and implicates its contribution in the pathogenesis of smoke-related lung diseases.

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Section: Discussionmentioning

confidence: 99%

Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells

Künzi

Holt

2019

Cell Death Discov.

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“…This is in agreement with ours and others' findings that PARP-1 level is increased during CS-induced DNA damage [47] – [51] , whereas conflicting results were obtained in other studies [52] , [53] . Nevertheless, the role of PARP-1 in DNA damage and repair during the pathogenesis of COPD is implicated [54] . A recent study has shown a physical association between p21 and PARP-1 [20] , implicating the regulation of p21-PARP-1 axis in CS-mediated DNA damage.…”

Section: Discussionmentioning

confidence: 99%

P21-PARP-1 Pathway Is Involved in Cigarette Smoke-Induced Lung DNA Damage and Cellular Senescence

et al. 2013

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Persistent DNA damage triggers cellular senescence, which may play an important role in the pathogenesis of cigarette smoke (CS)-induced lung diseases. Both p21CDKN1A (p21) and poly(ADP-ribose) polymerase-1 (PARP-1) are involved in DNA damage and repair. However, the role of p21-PARP-1 axis in regulating CS-induced lung DNA damage and cellular senescence remains unknown. We hypothesized that CS causes DNA damage and cellular senescence through a p21-PARP-1 axis. To test this hypothesis, we determined the levels of γH2AX (a marker for DNA double-strand breaks) as well as non-homologous end joining proteins (Ku70 and Ku80) in lungs of mice exposed to CS. We found that the level of γH2AX was increased, whereas the level of Ku70 was reduced in lungs of CS-exposed mice. Furthermore, p21 deletion reduced the level of γH2AX, but augmented the levels of Ku70, Ku80, and PAR in lungs by CS. Administration of PARP-1 inhibitor 3-aminobenzamide increased CS-induced DNA damage, but lowered the levels of Ku70 and Ku80, in lungs of p21 knockout mice. Moreover, 3-aminobenzamide increased senescence-associated β-galactosidase activity, but decreased the expression of proliferating cell nuclear antigen in mouse lungs in response to CS. Interestingly, 3-aminobenzamide treatment had no effect on neutrophil influx into bronchoalveolar lavage fluid by CS. These results demonstrate that the p21-PARP-1 pathway is involved in CS-induced DNA damage and cellular senescence.

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“…Furthermore, pre-incubation of PBMCs with UPF17 (4-methoxy- l -tyrosinyl-a- l -glutamyl- l -cysteinyl-glycine), a novel tetra peptide analog of glutathione (GSH), strongly reduced mRNA expression of PARP-1 in patients with COPD as compared to non-obstructive individuals. Interestingly, in non-obstructive smokers, higher PARP-1 activity was found as compared to patients with mild COPD ( 183 ). Overall, these two studies conducted on human samples strongly suggest occurrence of systemic oxidative stress induced DNA damage and PARP-1 activation in COPD pathogenesis.…”

Section: Parp In Copdmentioning

confidence: 99%

Poly(ADP-Ribose)Polymerase-1 in Lung Inflammatory Disorders: A Review

2017

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Asthma, acute lung injury (ALI), and chronic obstructive pulmonary disease (COPD) are lung inflammatory disorders with a common outcome, that is, difficulty in breathing. Corticosteroids, a class of potent anti-inflammatory drugs, have shown less success in the treatment/management of these disorders, particularly ALI and COPD; thus, alternative therapies are needed. Poly(ADP-ribose)polymerases (PARPs) are the post-translational modifying enzymes with a primary role in DNA repair. During the last two decades, several studies have reported the critical role played by PARPs in a good of inflammatory disorders. In the current review, the studies that address the role of PARPs in asthma, ALI, and COPD have been discussed. Among the different members of the family, PARP-1 emerges as a key player in the orchestration of lung inflammation in asthma and ALI. In addition, PARP activation seems to be associated with the progression of COPD. Furthermore, PARP-14 seems to play a crucial role in asthma. STAT-6 and GATA-3 are reported to be central players in PARP-1-mediated eosinophilic inflammation in asthma. Interestingly, oxidative stress–PARP-1–NF-κB axis appears to be tightly linked with inflammatory response in all three-lung diseases despite their distinct pathophysiologies. The present review sheds light on PARP-1-regulated factors, which may be common or differential players in asthma/ALI/COPD and put forward our prospective for future studies.

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Increased DNA Damage in Progression Of COPD: A Response By Poly(ADP-Ribose) Polymerase-1

Cited by 16 publications

References 35 publications

Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells

Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells

P21-PARP-1 Pathway Is Involved in Cigarette Smoke-Induced Lung DNA Damage and Cellular Senescence

Poly(ADP-Ribose)Polymerase-1 in Lung Inflammatory Disorders: A Review

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