Deregulation of apoptosis mediators' p53 and bcl2 in lung tissue of COPD patients.
Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis. However, studies in human subjects are limited. p53 and bcl2 protein expression was measured by western blot on lung tissue specimens from 43 subjects (23 COPD smokers and 20 non-COPD smokers), using beta-actin as internal control. Additionally, p53 and bcl2 expression patterns were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same individuals. Western blot analysis showed statistically significant increased p53 protein levels in COPD smokers in comparison with non-COPD smokers (p = 0.038), while bcl2 protein levels were not statistically different between the two groups. Lung immunohistochemistry showed increased ratio of positive p53-stained type II pneumocytes/total type II pneumocytes in COPD smokers compared to non-COPD smokers (p = 0.01), whereas the p53 staining ratio in alveolar macrophages and in lymphocyte-like cells did not differ statistically between the two groups. On the other hand, bcl2 expression did not differ between the two groups in all three cell types. The increased expression of pro-apoptotic p53 in type II pneumocytes of COPD patients not counterbalanced by the anti-apoptotic bcl2 could reflect increased apoptosis in the alveolar epithelium of COPD patients. Our results confirm previous experiments and support the hypothesis of a disturbance in the balance between the pro- and anti-apoptotic mediators in COPD.
Siganaki
Marianna
M
Laboratory of Molecular and Cellular Pulmonology, Medical School University of Crete, Greece.
Koutsopoulos
Anastasios V
AV
Neofytou
Eirini
E
Vlachaki
Eleni
E
Psarrou
Maria
M
Soulitzis
Nikolaos
N
Pentilas
Nikolaos
N
Schiza
Sophia
S
Siafakas
Nikolaos M
NM
Tzortzaki
Eleni G
EG
D000368:Aged; D056809:Alveolar Epithelial Cells / Q000737:chemistry / Q000473:pathology; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry* / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry / Q000473:pathology; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D012907:Smoking; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D015854:Up-Regulation
D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53