ABSTRACT
Increased oxidative stress (OS) and systemic inflammation are key players in the pathophysiology of chronic obstructive pulmonary disease (COPD). We aimed to clarify the effects of synthetic glutathione (GSH) analogue peptides UPF1 and UPF17 on the mRNA levels of enzymes involved in systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs) from patients with acute exacerbation of COPD (AE-COPD) and stable COPD along with non-obstructive smokers and non-smokers. UPF1 and UPF17 increased the expression of enzymes involved in the formation of the antioxidant capacity: superoxide dismutase 1 (SOD1) and the catalytic subunit of glutamyl-cysteine ligase (GCLC) in patients with AE-COPD and stable COPD, but also in non-obstructive smokers and non-smokers. Similarly, both UPF1 and UPF17 increased the expression of inflammatory enzymes poly(ADP-ribose) polymerase-1 (PARP-1), dipeptidyl peptidase 4 (DPP4), and cyclooxygenase-2 (COX-2). Both UPF analogues acted in a gender-dependent manner by increasing the expression of certain anti-inflammatory (histone deacetylase 2 (HDAC2)) and GSH metabolism pathway (SOD1 and GSH reductase (GSR))-related enzymes in females and decreasing them in males. UPF1 and UPF17 are able to increase the expression of the enzymes involved in GSH metabolism and could serve as a lead for designing potential COPD therapies against excessive OS.
ABSTRACT
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 (ORâ=â1.01; 95%; p<0.001). An antioxidant tetrapeptide UPF17 significantly reduced the PARP-1 mRNA expression in COPD, compared to that in non-obstructive individuals (pâ=â0.040). 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.
Subject(s)
DNA Damage/genetics , Poly(ADP-ribose) Polymerases/metabolism , Pulmonary Disease, Chronic Obstructive/genetics , Aged , Comet Assay , Female , Humans , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Poly (ADP-Ribose) Polymerase-1ABSTRACT
Ce document est un rapport réalisé par différentes agences des Nations Unies suite au séisme qui a touché Haïti en janvier 2010, au sujet des problématiques interdépendantes de la gestion des décombres, du logement, de la création d'emplois à long termes et des emplois à haute intensité de main d'£uvre.
Subject(s)
Post Disaster Reconstruction , HaitiABSTRACT
Previously the authors have designed and synthesized a library of antioxidative glutathione analogues called UPF peptides which are superior to glutathione in hydroxyl radical elimination. This paper is a follow-up study which investigated the effects of the most promising members of the library (UPF1 and UPF17) on oxidative stress-related enzymes. At concentrations used in vivo experiments neither UPF peptide influenced the activity of glutathione peroxidase (GPx) when purified enzyme or erythrocyte lysate was used. At higher concentrations they inhibited GPx activity. UPF peptides had no effect on glutathione reductase (GR) activity. Also they, as well as glutathione itself, slightly increased MnSOD activity in human brain mitochondria and inhibited oxidative burst caused by neutrophil NAD(P)H oxidase. RT-PCR measurements showed that UPF1 and UPF17 have no effect on GPx and MnSOD expression level in human blood mononuclear cells. The results of this study confirm that investigated UPF peptides do not interfere with the enzymatic mechanisms of antioxidative defence and can be used as themselves or as a lead for the protector molecule design against excessive oxidative stress.
Subject(s)
Antioxidants/pharmacology , Glutathione/analogs & derivatives , Oxidative Stress/drug effects , Brain/drug effects , Brain/enzymology , Free Radicals/metabolism , Glutathione/pharmacology , Glutathione Peroxidase/drug effects , Glutathione Peroxidase/metabolism , Glutathione Reductase/drug effects , Glutathione Reductase/metabolism , Humans , Leukocytes, Mononuclear/drug effects , Mitochondria/drug effects , Mitochondria/enzymology , NADPH Oxidases/metabolism , Oxidative Stress/physiology , Peptide Library , Reverse Transcriptase Polymerase Chain Reaction , Superoxide Dismutase/drug effects , Superoxide Dismutase/metabolismABSTRACT
Publicación que recoge tanto experiencias con sindicatos como estudios de caso de acción sindical. Incluye también un repertorio de recomendaciones prácticas de la OIT sobre el VIH/SIDA y el mundo del trabajo.
Subject(s)
HIV Infections , Acquired Immunodeficiency SyndromeABSTRACT
La presente publicación incluye dos estudios que abordan desde diferentes perspectivas la exclusión de los pueblos indígenas en los procesos para alcanzar los ODM. Una aproximación a la brecha segun la condición étnico-linguística de la población. El primer trabajo destaca la situación de los pueblos indígenas y originarios con relación a los compromisos universales del desarrollo humano establecidos en los ODM. El segundo estudio examina las condiciones para lograr los ODM en la Comunidad Indígena Jathun Ayllu Amarete sobre la base de la información proporcionada por las autoridades indígenas tradicionales y las entidades públicas asentadas en Amarete.
ABSTRACT
La elaboración del plan propone erradicar el trabajo infantil con el apoyo de las instancias gubernamentales y organizaciones vinculadas al trabajo infantil.El objetivo contribuir a reducir drásticamente el trabajo de niños menores de 14 años y a proteger social y laboralmente a los adolescentes trabajadores mayores de 14 años
Subject(s)
Humans , ChildABSTRACT
Reune información que forma parte de la Salud y la Seguridad en el Trabajo: colección de módulos editado por la Oficina de Actividades para los Trabajadores ACTRAV de la OIT como material que se presentó en el taller realizado en Las Parejas, Santa Fe, Argentina del 16 al 19 de noviembre de 2004
Subject(s)
Chemical Contamination , Ergonomics , Impacts of Polution on Health , United NationsABSTRACT
Reune información que forma parte de la Salud y la Seguridad en el Trabajo: colección de módulos editado por la Oficina de Actividades para los Trabajadores ACTRAV de la OIT como material que se presentó en el taller realizado en Las Parejas, Santa Fe, Argentina del 16 al 19 de noviembre de 2004
Subject(s)
Impacts of Polution on Health , Chemical Contamination , Ergonomics , United NationsSubject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Mass Media , Homemaker Services , United Nations , Brazil , Child Advocacy , Sex Factors , Journalism , Public Policy , Editorial Policies , Information SystemsABSTRACT
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