Poly(ADP-ribosyl)ation is a survival mechanism in cigarette smoke-induced and hydrogen peroxide-mediated cell death

Kovács, Katalin; Erdélyi, Katalin; Hegedűs, Csaba; Lakatos, Petra; Regdon, Zsolt; Bai, Péter; Haskó, György; Szabó, Éva; Virág, László

doi:10.1016/j.freeradbiomed.2012.08.579

Cited by 25 publications

(26 citation statements)

References 26 publications

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“…Thousands of compounds are present in CS, including a large number of reactive oxygen species that can cause DNA damage and lead to the activation of poly (ADP-ribose) polymerase (PARP) enzyme [36]. Other components of CS, such as nicotine and acrolein, have also been shown to exert direct genotoxic effects [37,38].…”

Section: Discussionmentioning

confidence: 99%

The standardized herbal formula, PM014, ameliorated cigarette smoke-induced lung inflammation in a murine model of chronic obstructive pulmonary disease

Jung

Haam

Park

et al. 2013

BMC Complement Altern Med

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BackgroundIn this study, we evaluated the anti-inflammatory effect of PM014 on cigarette smoke induced lung disease in the murine animal model of chronic obstructive pulmonary disease (COPD).MethodsMice were exposed to cigarette smoke (CS) for 2 weeks to induce COPD-like lung inflammation. Two hours prior to cigarette smoke exposure, the treatment group was administered PM014 via an oral injection. To investigate the effects of PM014, we assessed PM014 functions in vivo, including immune cell infiltration, cytokine profiles in bronchoalveolar lavage (BAL) fluid and histopathological changes in the lung. The efficacy of PM014 was compared with that of the recently developed anti-COPD drug, roflumilast.ResultsPM014 substantially inhibited immune cell infiltration (neutrophils, macrophages, and lymphocytes) into the airway. In addition, IL-6, TNF-α and MCP-1 were decreased in the BAL fluid of PM014-treated mice compared to cigarette smoke stimulated mice. These changes were more prominent than roflumilast treated mice. The expression of PAS-positive cells in the bronchial layer was also significantly reduced in both PM014 and roflumilast treated mice.ConclusionsThese data suggest that PM014 exerts strong therapeutic effects against CS induced, COPD-like lung inflammation. Therefore, this herbal medicine may represent a novel therapeutic agent for lung inflammation in general, as well as a specific agent for COPD treatment.

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Section: Discussionmentioning

confidence: 99%

The standardized herbal formula, PM014, ameliorated cigarette smoke-induced lung inflammation in a murine model of chronic obstructive pulmonary disease

Jung

Haam

Park

et al. 2013

BMC Complement Altern Med

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“…Generation of large amounts of ROS can overwhelm the intracellular antioxidant defense, causing lipid peroxidation, protein modification, and DNA breaks [2]. It is known that ROS-induced depletion of antioxidants is a key factor for the initiation of atherosclerosis and the development of CVD [3].…”

Section: Introductionmentioning

confidence: 99%

Effects of Methanol Extract of Breadfruit (Artocarpus altilis) on Atherogenic Indices and Redox Status of Cellular System of Hypercholesterolemic Male Rats

Adaramoye

Akanni

2014

Advances in Pharmacological Sciences

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We investigated the effects of methanol extract of Artocarpus altilis (AA) on atherogenic indices and redox status of cellular system of rats fed with dietary cholesterol while Questran (QUE) served as standard. Biochemical indices such as total cholesterol (TC), triglycerides (TG), low- and high-density lipoproteins-cholesterol (LDL-C and HDL-C), aspartate and alanine aminotransferases (AST and ALT), lactate dehydrogenase (LDH), reduced glutathione, glutathione-s-transferase, glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation (LPO) were assessed. Hypercholesterolemic (HC) rats had significantly increased relative weight of liver and heart. Dietary cholesterol caused a significant increase (P < 0.05) in the levels of serum, hepatic, and cardiac TC by 110%, 70%, and 85%, LDL-C by 79%, 82%, and 176%, and TG by 68%, 96%, and 62%, respectively. Treatment with AA significantly reduced the relative weight of the organs and lipid parameters. There were beneficial increases in serum and cardiac HDL-C levels in HC rats treated with AA. In HC rats, serum LDH, ALT, and AST activities and levels of LPO were increased, whereas hepatic and cardiac SOD, CAT, and GPx were reduced. All biochemical and histological alterations were ameliorated upon treatment with AA. Extract of AA had protective effects against dietary cholesterol-induced hypercholesterolemia.

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“…The DNA damage along with PARP activity and PARP-1 mRNA expression has not been investigated formerly in this way. In-vitro studies have shown relations of PARP activity and cigarette smoke [19], [20]. Also, differential activation of PARP in PBMC from controls and COPD patients has been shown previously [7], but in-vivo studies on the relationships between PARP activity and COPD progression have not been performed before.…”

Section: Discussionmentioning

confidence: 96%

“…This suggests that although PARP is a very important player in the DNA repair, it does not represent the only pathway to prevent smokers from developing COPD. In mammalian cells, the basal enzymatic activity of PARP is very low, but oxidative and nitrosative stress can trigger DNA strand breakage, which in turn abruptly stimulates the PARP-1 activity [20], [25]–[27]. Moderate activation of PARP is of physiological importance and could be beneficial via facilitating the DNA repair.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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Chronic oxidative stress (OS), a major mechanism of chronic obstructive pulmonary disease (COPD), may cause significant damage to DNA. Poly(ADP-ribose) polymerase (PARP)-1 is rapidly activated by OS-induced DNA lesions. However, the degree of DNA damage along with the evolution of COPD is unclear. In peripheral blood mononuclear cells of non-smoking individuals, non-obstructive smokers, patients with COPD of all stages and those with COPD exacerbation, we evaluated DNA damage, PARP activity and PARP-1 mRNA expression using Comet Assay IV, biotinylated-NAD incorporation assay and qRT-PCR, respectively and subjected results to ordinal logistic regression modelling. Adjusted for demographics, smoking-related parameters and lung function, novel comet parameters, tail length/cell length ratio and tail migration/cell length ratio, showed the greatest increase along the study groups corresponding to the evolution of COPD [odds ratio (OR) 7.88, 95% CI 4.26–14.57; p<0.001 and OR 3.91, 95% CI 2.69–5.66; p<0.001, respectively]. Analogously, PARP activity increased significantly over the groups (OR = 1.01; 95%; p<0.001). An antioxidant tetrapeptide UPF17 significantly reduced the PARP-1 mRNA expression in COPD, compared to that in non-obstructive individuals (p = 0.040). Tail length/cell length and tail migration/cell length ratios provide novel progression-sensitive tools for assessment of DNA damage. However, it remains to be elucidated whether inhibition of an elevated PARP-1 activity has a safe enough potential to break the vicious cycle of the development and progression of COPD.

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Poly(ADP-ribosyl)ation is a survival mechanism in cigarette smoke-induced and hydrogen peroxide-mediated cell death

Cited by 25 publications

References 26 publications

The standardized herbal formula, PM014, ameliorated cigarette smoke-induced lung inflammation in a murine model of chronic obstructive pulmonary disease

The standardized herbal formula, PM014, ameliorated cigarette smoke-induced lung inflammation in a murine model of chronic obstructive pulmonary disease

Effects of Methanol Extract of Breadfruit (Artocarpus altilis) on Atherogenic Indices and Redox Status of Cellular System of Hypercholesterolemic Male Rats

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

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