Luiz Philippe S Sergio1, Leda M F Lucinda2,3,4, Maycon M Reboredo2,3, Flavia de Paoli3,4, Lídia M C Fonseca2,3, Bruno V Pinheiro2,3, Andre L Mencalha1, Adenilson S Fonseca1,5. 1. a Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes , Universidade do Estado do Rio de Janeiro , Vila Isabel , Rio de Janeiro , Brazil. 2. b Laboratório de Pesquisa em Pneumologia , Universidade Federal de Juiz de Fora , Dom Bosco, Juiz de Fora , Minas Gerais , Brazil. 3. c Centro de Biologia da Reprodução , Universidade Federal de Juiz de Fora , Campus Universitário, São Pedro, Juiz de Fora , Minas Gerais , Brazil. 4. d Departamento de Morfologia , Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora , Campus Universitário, São Pedro, Juiz de Fora , Minas Gerais , Brazil. 5. e Centro de Ciências da Saúde , Centro Universitário Serra dos Órgãos , Teresópolis , Rio de Janeiro , Brazil.
Abstract
Purpose/Aim of the study: Patients suffering from chronic obstructive pulmonary disease (COPD) in association with acute respiratory distress syndrome (ARDS) present oxidative stress in lung cells, with production of free radicals and DNA lesions in pulmonary and adjacent cells. Once the DNA molecule is damaged, a set of enzymatic mechanisms are trigged to preserve genetic code integrity and cellular homeostasis. These enzymatic mechanisms include the base and the nucleotide excision repair pathways, as well as telomere regulation. Thus, the aim of this work was to evaluate the mRNA levels from APEX1, ERCC2, TP53, and TRF2 genes in lung tissue from Wistar rats affected by acute lung injury in response to sepsis and emphysema. MATERIALS AND METHODS: Adult male Wistar rats were randomized into 4 groups (n = 6, for each group): control, emphysema, sepsis, and emphysema with sepsis. Pulmonary emphysema was induced by intratracheal instillation of elastase (12 IU/animal) and sepsis induced by intraperitoneal Escherichia coli lipopolysaccharide (LPS) injection (10 mg/kg). Lungs were removed, and samples were withdrawn for histological analysis and total RNA extraction, cDNA synthesis, and mRNA level evaluation by real time quantitative polymerase chain reaction. RESULTS: Data show acute lung injury by LPS and emphysema by elastase and that APEX1, ERCC2, TP53, and TRF2 mRNA levels are increased significantly (p < 0.01) in emphysema with sepsis group. CONCLUSION: Our results suggest that alteration in mRNA levels from DNA repair and genomic stability could be part of cell response to acute lung injury in response to emphysema and sepsis.
Purpose/Aim of the study: Patients suffering from chronic obstructive pulmonary disease (COPD) in association with acute respiratory distress syndrome (ARDS) present oxidative stress in lung cells, with production of free radicals and DNA lesions in pulmonary and adjacent cells. Once the DNA molecule is damaged, a set of enzymatic mechanisms are trigged to preserve genetic code integrity and cellular homeostasis. These enzymatic mechanisms include the base and the nucleotide excision repair pathways, as well as telomere regulation. Thus, the aim of this work was to evaluate the mRNA levels from APEX1, ERCC2, TP53, and TRF2 genes in lung tissue from Wistar rats affected by acute lung injury in response to sepsis and emphysema. MATERIALS AND METHODS: Adult male Wistar rats were randomized into 4 groups (n = 6, for each group): control, emphysema, sepsis, and emphysema with sepsis. Pulmonary emphysema was induced by intratracheal instillation of elastase (12 IU/animal) and sepsis induced by intraperitoneal Escherichia coli lipopolysaccharide (LPS) injection (10 mg/kg). Lungs were removed, and samples were withdrawn for histological analysis and total RNA extraction, cDNA synthesis, and mRNA level evaluation by real time quantitative polymerase chain reaction. RESULTS: Data show acute lung injury by LPS and emphysema by elastase and that APEX1, ERCC2, TP53, and TRF2 mRNA levels are increased significantly (p < 0.01) in emphysema with sepsis group. CONCLUSION: Our results suggest that alteration in mRNA levels from DNA repair and genomic stability could be part of cell response to acute lung injury in response to emphysema and sepsis.
Entities:
Keywords:
DNA repair; acute lung injury; emphysema; genomic stability; sepsis