Increased PARP Activity and DNA Damage in NSCLC Patients: The Influence of COPD

(1) Background: Lung cancer (LC) is a major leading cause of death worldwide. Poly (ADP-ribose) polymerase (PARP)-1 and PARP-2 are key players in cancer. We aimed to assess PARP-1 and PARP-2 expression and activity and DNA damage in tumors and non-tumor lungs from patients with/without chronic obstructive pulmonary disease (COPD). (2) Methods: Lung tumor and non-tumor specimens were obtained through video-assisted thoracoscopic surgery (VATS) in LC patients with/without underlying COPD (two groups of patients, n = 15/group). PARP-1 and PARP-2 expression (ELISA), PARP activity (PARP colorimetric assay kit) and DNA damage (immunohistochemistry) levels were identified in all samples. (3) Results: Both PARP-1 and PARP-2 expression levels were significantly lower in lung tumors (irrespective of COPD)compared to non-tumor specimens, while DNA damage and PARP activity levels significantly increased in lung tumors compared to non-tumor specimens only in LC-COPD patients. PARP-2 expression was positively correlated with smoking burden in LC-COPD patients. (4) Conclusions: In lung tumors of COPD patients, an overactivation of PARP enzyme was observed. A decline in PARP-1 and PARP-2 protein expression was seen in lung tumors irrespective of COPD. Other phenotypic features (airway obstruction) beyond cancer may account for the increase in PARP activity seen in the tumors of patients with underlying COPD.

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Impact of Previous Physical Activity Levels on Symptomatology, Functionality, and Strength during an Acute Exacerbation in COPD Patients

Healthcare ◽

10.3390/healthcare6040139 ◽

2018 ◽

Vol 6 (4) ◽

pp. 139 ◽

Cited By ~ 2

Author(s):

Laura López-López ◽

Irene Torres-Sánchez ◽

Ramón Romero-Fernández ◽

María Granados-Santiago ◽

Janet Rodríguez-Torres ◽

...

Keyword(s):

Physical Activity ◽

Observational Study ◽

Exercise Capacity ◽

Functional Independence Measure ◽

Functional Independence ◽

Chronic Obstructive ◽

Activity Levels ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Hospital Patients

The main objective of this study is to determine the relationship between physical activity (PA) level prior to hospitalization and the pulmonary symptomatology, functionality, exercise capacity, and strength of acute exacerbated chronic obstructive pulmonary disease (COPD) patients. In this observational study, all data were taken during the patient’s first day in hospital. Patients were divided into two groups (a PA group, and a physical inactivity (PI) group), according to the PA level evaluated by the Baecke questionnaire. Cough status was evaluated by the Leicester Cough Questionnaire (LCQ), and dyspnea was assessed using the modified Medical Research Council dyspnea scale (mMRC). Functionality was measured by the Functional Independence Measure (FIM) and the London Chest Activity of Daily Living scale (LCADL). Exercise capacity was evaluated by the two-minute step-in-place (2MSP) test, and strength assessed by dynamometry. A total of 151 patients were included in this observational study. Patients in the PI group obtained worse results compared to the PA group, and significant differences (p < 0.05) were found in all of the variables. Those COPD patients who regularly perform PA have less dyspnea and cough, as well as better functionality, exercise capacity and strength during an exacerbation, without relationship to the severity of the pathology.

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High Vegetables Intake and Response to COPD Rehabilitation. The Role of Oxidative Stress, Inflammation and Dna Damage.

10.20944/preprints202106.0558.v1 ◽

2021 ◽

Author(s):

Sara Ilari ◽

Laura Vitiello ◽

Patrizia Russo ◽

Stefania Proietti ◽

Mirta Milic ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Pulmonary Rehabilitation ◽

Vegetable Consumption ◽

Natural Antioxidants ◽

Lung Parenchyma ◽

Normal Diet ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

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Daily Vegetables Intake and Response to COPD Rehabilitation. The Role of Oxidative Stress, Inflammation and DNA Damage

Nutrients ◽

10.3390/nu13082787 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2787

Author(s):

Sara Ilari ◽

Laura Vitiello ◽

Patrizia Russo ◽

Stefania Proietti ◽

Mirta Milić ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Pulmonary Rehabilitation ◽

Vegetable Intake ◽

Vegetable Consumption ◽

Natural Antioxidants ◽

Lung Parenchyma ◽

Normal Diet ◽

Chronic Obstructive ◽

Copd Patients

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to reduce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and reduction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Recently, also natural antioxidants have been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measurements at baseline and after completion of the three weeks PR. We found that daily vegetable intake in normal diet, without any specific intervention, can increase the probability to successfully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of non-responders, p = 0.033). The association was especially evident in subjects ≥ 80 year of age (OR = 17.0; p < 0.019). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an improvement in the patient’s inflammatory state.

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Effect of Physical Exercise on the Level of DNA Damage in Chronic Obstructive Pulmonary Disease Patients

ISRN Pulmonology ◽

10.1155/2013/907520 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Andréa Lúcia G. da Silva ◽

Helen T. da Rosa ◽

Eduarda Bender ◽

Paulo Ricardo da Rosa ◽

Mirian Salvador ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Lipid Peroxidation ◽

Dna Damage ◽

Dna Repair ◽

Physical Exercise ◽

Pulmonary Disease ◽

Peripheral Blood ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients

This study assessed the chronic effects of physical exercise on the level of DNA damage and the susceptibility to exogenous mutagens in peripheral blood cells of chronic obstructive pulmonary disease (COPD) patients. The case-control study enrolled COPD patients separated into two groups (group of physical exercise (PE-COPD; n=15); group of nonphysical exercise (COPD; n=36)) and 51 controls. Peripheral blood was used to evaluate DNA damage by comet assay and lipid peroxidation by measurement of thiobarbituric acid reactive species (TBARS). The cytogenetic damage was evaluated by the buccal micronucleus cytome assay. The results showed that the TBARS values were significantly lower in PE-COPD than in COPD group. The residual DNA damage (induced by methyl methanesulphonate alkylating agent) in PE-COPD was similar to the controls group, in contrast to COPD group where it was significantly elevated. COPD group showed elevated frequency of nuclear buds (BUD) and condensed chromatin (CC) in relation to PE-COPD and control groups, which could indicate a deficiency in DNA repair and early apoptosis of the damaged cells. We concluded that the physical exercise for COPD patients leads to significant decrease of lipid peroxidation in blood plasma, decrease of susceptibility to exogenous mutagenic, and better efficiency in DNA repair.

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Immune Cell Subtypes and Cytokines in Lung Tumor Microenvironment: Influence of COPD

Cancers ◽

10.3390/cancers12051217 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1217 ◽

Cited By ~ 2

Author(s):

Jun Tang ◽

Daniel Ramis-Cabrer ◽

Víctor Curull ◽

Xuejie Wang ◽

Liyun Qin ◽

...

Keyword(s):

Interferon Gamma ◽

Plasma Cells ◽

Immune Cell ◽

Lung Tumor ◽

Tumor Resection ◽

Chronic Obstructive ◽

Igg Antibody ◽

Immune Profile ◽

Cell Counts ◽

Copd Patients

Background: The immune microenvironment plays a role in tumorigenesis. Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for lung cancer (LC). We hypothesized that immune profile characterized by T regulatory (Treg), natural killer (NK), and plasma cells, as well as interleukin (IL)-10 and interferon-gamma, may differ within tumors of LC patients with/without COPD. Methods: Treg (anti-CD3 and anti-forkhead boxP3 antibodies), NK (anti-NCR1 antibody), IgG (anti-CD138-IgG antibody), IgA (anti-CD138-IgA antibody) using immunohistochemistry, and both IL-10 and interferon-gamma (ELISA) were quantified in tumor and non-tumor specimens (thoracotomy for lung tumor resection) from 33 LC–COPD patients and 20 LC-only patients. Results: Immune profile in tumor versus non-tumor specimens: Treg cell counts significantly increased in tumors of both LC and LC–COPD patients, while in tumors of the latter group, IgG-secreting plasma cells significantly decreased and IL-10 increased. No significant differences were seen in levels of NK cells, IgA-secreting cells, IgA/IgG, or interferon-gamma. Immune profile in tumors of LC–COPD versus LC: No significant differences were observed in tumors between LC–COPD and LC patients for any study marker. Conclusions: Immune cell subtypes and cytokines are differentially expressed in lung tumors, and the presence of COPD elicited a decline in IgG-secreting plasma cell levels but not in other cell types.

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DNA damage and cellular abnormalities in tuberculosis, lung cancer and chronic obstructive pulmonary disease

Multidisciplinary Respiratory Medicine ◽

10.4081/mrm.2015.344 ◽

2015 ◽

Vol 10 ◽

Author(s):

Andréa Lúcia Gonçalves da Silva ◽

Maribel Josimara Bresciani ◽

Thaís Evelyn Karnopp ◽

Augusto Ferreira Weber ◽

Joel Henrique Ellwanger ◽

...

Keyword(s):

Lung Cancer ◽

Dna Damage ◽

Low Frequency ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Chronic Obstructive Pulmonary Diseases ◽

Cellular Abnormalities ◽

Apoptosis And Necrosis ◽

Cytome Assay

Background: Tuberculosis (TB), Lung Cancer (LC) and Chronic Obstructive Pulmonary Diseases (COPD) affect millions of individuals worldwide. Monitoring of DNA damage in pathological situations has been investigated because it can add a new dimension to clinical expression and may represent a potential target for therapeutic intervention. The aim of this study was to evaluate DNA damage and the frequency of cellular abnormalities in TB, LC and COPD patients by comparing them to healthy subjects. Methods: The detection of DNA damage by a buccal micronucleus cytome assay was investigated in patients with COPD (n = 28), LC (n = 18) and TB (n = 22) and compared to control individuals (n = 17). Results: The COPD group had a higher frequency of apoptotic cells compared to TB and LC group. The TB group showed a higher frequency of DNA damage, defect in cytokinesis, apoptotic and necrotic cells. Patients with LC had low frequency of chromosomal aberrations than TB and COPD patients. Conclusion: COPD patients showed cellular abnormalities that corresponded to cell death by apoptosis and necrosis, while patients with TB presented defects in cytokinesis and dysfunctions in DNA repair that resulted in the formation of micronucleus (MN) besides apoptotic and necrotic cells. Patients with COPD, TB and LC had a low frequency of permanent DNA damage.

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High Vegetables Intake and Response to COPD Rehabilitation Treatment. The Role of Oxidative Stress, Inflammation and DNA Damage

10.20944/preprints202106.0112.v1 ◽

2021 ◽

Author(s):

Sara Ilari ◽

Laura Vitiello ◽

Patrizia Russo ◽

Stefania Proietti ◽

Mirta Milic ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Pulmonary Rehabilitation ◽

Vegetable Consumption ◽

Natural Antioxidants ◽

Lung Parenchyma ◽

Normal Diet ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients

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Automodified Poly(ADP-Ribose) Polymerase Analysis to monitor DNA Damage in Peripheral Lymphocytes of Floricoltorists occupationally exposed to Pesticides

10.20944/preprints201901.0019.v1 ◽

2019 ◽

Author(s):

Serena Imperato ◽

Carmela Mistretta ◽

Maria Marone ◽

Ilaria Migliaccio ◽

Ilaria Pulcinelli ◽

...

Keyword(s):

Dna Damage ◽

Genotoxic Stress ◽

Polymerase Activity ◽

Peripheral Blood Lymphocytes ◽

Activity Levels ◽

Strand Breaks ◽

Non Invasive ◽

Occupationally Exposed ◽

Parp Activity ◽

Dna Strand

Background: Increased DNA damage and the propension to cancer development, depend on the modulation of the mechanisms to control and maintain genomic integrity. Poly(ADP-Ribose)Polymerase activation and automodification are early responses to genotoxic stress. Upon binding to DNA strand breaks, the enzyme, a molecular DNA nick sensor, is hyperactivated: this is the first step in a series of events leading to either DNA repair or apoptosis. Enzyme hyperactivation and automodification can be easily measured and are widely used to look at DNA damage extent in the cell. We investigated whether these two markers (increased catalytic activity and auto modification), could help to monitor DNA damage in lymphocytes of flower growers from Southern Italy, occupationally exposed to pesticides. Methods: Peripheral lymphocyte lysates were analysed for Poly(ADP-Ribose) Polymerase activity, and by SDS-PAGE and anti-Poly(ADP-Ribose)Polymerase 1-antibody to measure automodified anti-Poly(ADP-Ribose) Polymerase levels by densitometry. Results: Poly(ADP-Ribose)Polymerase activity levels were consistent with those of enzyme auto-modification. Growers daily exposed to pesticides, showed both biomarkers very high, either in the presence or in the absence of pathologies. Conclusions: PARP activity and auto-modification in peripheral blood lymphocytes are possible,non-invasive, and routinar tools to monitor the healthy conditions of floricoltorists.

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DNA Damage and Oxidative Stress in Patients with Chronic Obstructive Pulmonary Disease

The Open Biomarkers Journal ◽

10.2174/1875318301306010001 ◽

2013 ◽

Vol 6 (1) ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Andréa Lúcia G da Silva ◽

Helen T da Rosa ◽

Clara F Charlier ◽

Miriam Salvador ◽

Dinara J Moura ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Obstructive Pulmonary Disease ◽

Dna Damage ◽

Comet Assay ◽

Blood Plasma ◽

Peripheral Blood ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Exogenous Dna ◽

Copd Patients

Background: We aimed to assess the level of DNA damage and susceptibility to exogenous mutagens in peripheral blood cells of Chronic Obstructive Pulmonary Disease (COPD) patients and healthy individuals by comet assay. Oxidative stress was also evaluated by means of thiobarbituric acid reactive species (TBARS) in blood plasma. Methods: Case-control study enrolling 51 COPD patients and 51 controls. Peripheral blood was used to perform the alkaline (pH>13) and neutral (pH=8.5) comet assay. For the assessment of susceptibility to exogenous DNA damage, the cells were treated with methylmethane sulfonate (MMS) for 1-hour or 3-hour at 37° C. The percentage of residual DNA damage after 3-h MMS treatment was calculated using the value of 1-h MMS treatment for each subject as 100%. Lipid peroxidation was evaluated by measuring TBARS in blood plasma. Results: DNA damage in patients was significantly higher than in controls as measured by the neutral and alkaline comet assay. Residual DNA damage detected after MMS treatment increased in patients, in contrast to controls, indicating higher susceptibility to alkylation damage and/or repair inhibition. High susceptibility to exogenous DNA damage in COPD patients correlates with high amount of TBARS and low forced vital capacity and expiratory volume. Conclusion: The positive correlation between increased susceptibility to exogenous DNA damage and TBARS levels in COPD patients suggests the possible involvement of oxidative stress in damage induction and/or repair inhibition.

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DNA damage and repair capacity in lymphocyte of chronic obstructive pulmonary diseases patients during physical exercise with oxygen supplementation

Multidisciplinary Respiratory Medicine ◽

10.4081/mrm.2016.349 ◽

2016 ◽

Vol 11 ◽

Author(s):

Andréa Lúcia Gonçalves da Silva ◽

Thaís Evelyn Karnopp ◽

Augusto Ferreira Weber ◽

Cassia da Luz Goulart ◽

Paloma de Borba Scheneiders ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Physical Exercise ◽

Aerobic Exercise ◽

Pulmonary Diseases ◽

Chronic Obstructive ◽

Oxygen Supplementation ◽

Repair Capacity ◽

Copd Patients ◽

Chronic Obstructive Pulmonary Diseases

Background: We hypothesized that the use of oxygen supplementation during aerobic exercise induces less DNA damage than exercise alone. The aim of this study is to assess the level of DNA damage induced by physical exercise with and without oxygen supplementation in chronic obstructive pulmonary diseases (COPD) patients. Methods: Peripheral blood was collected before and after aerobic exercise in two conditions: (I) aerobic exercise without oxygen supplementation (AE group) and (II) with oxygen supplementation (AE-O2 group). Lymphocytes were collected to perform the alkaline version of the Comet Assay. To assess the susceptibility to exogenous DNA damage, the lymphocytes were treated with methyl methanesulphonate (MMS) for 1-h or 3-h. After 3-h treatment, the percentage of residual damage was calculated assuming the value of 1-h MMS treatment as 100%. Results: AE group showed lower induced damage (1 h of MMS treatment) and consequently less DNA repair compared to AE-O2 group. AE-O2 group showed an increase in the induced DNA damage (1 h of MMS treatment) and an increased DNA repair capacity. Within the AE-O2 group, in the post-exercise situation the induced DNA damage after 1 h of MMS treatment was higher (p = 0.01) than in the pre-exercise. Conclusion: COPD patients who performed physical exercise associated with oxygen supplementation had a better response to DNA damage induced by MMS and a better DNA repair when compared to the condition of physical exercise without oxygen supplementation.Trial registration: UNISC N374.298. Registered 04 JUN 2013 (retrospectively registered).

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