scholarly journals Protective effect of autophagy on endoplasmic reticulum stress induced apoptosis of alveolar epithelial cells in rat models of COPD

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Yao Tang ◽  
Qi-Hang Cai ◽  
Yong-Jian Wang ◽  
Shao-Hua Fan ◽  
Zi-Feng Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Caspase 3 ◽  
Intervention Group ◽  
Alveolar Epithelial Cells ◽  
Beclin 1 ◽  
Control Group ◽  
Rat Models ◽  
Alveolar Epithelial ◽  
Induced Apoptosis

During the present study, we explored the protective effects of autophagy on endoplasmic reticulum (ER) stress (ERS) induced apoptosis belonging to alveolar epithelial cells (AECs) in rat models with chronic obstructive pulmonary disease (COPD). Fifty-six 12-week-old male Sprague–Dawley (SD) rats were randomly assigned into the COPD group (rats exposed to cigarette smoke (CS)), the 3-methyladenine (3-MA) intervention group (COPD rats were administrated with 10 mg/kg autophagy inhibitors), the chloroquine (CQ)-intervention group (COPD rats were administrated 40 mg/kg CQ), and the control group (rats breathed in normal saline). The forced expiratory volume in 0.3 s/forced vital capacity (FEV0.3/FVC%), inspiratory resistance (RI), and dynamic lung compliance (Cdyn) were measured and recorded. The expressions of PKR-like ER kinase (PERK) and CCAAT/enhancer-binding protein-homologous protein (CHOP) were detected by immunohistochemistry. The cell apoptotic rates of AECs were analyzed by terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick end-labeling (TUNEL) staining. The expression levels of light chain 3 (LC3-II), p62, Beclin-1, ATG5, ATG7, Caspase-12, and Caspase-3 were detected by Western blotting. Results showed that the COPD group exhibited a lower FEV0.3/FVC% and Cdyn, and a higher RI than the control group. Compared with the control group, the integrated optical density (IOD) values of PERK and CHOP, the apoptotic rate of AECs, and expressions of LC3-II, Beclin-1, ATG5, ATG7, Caspase-3, and Caspase-12 expressions were significantly higher, whereas p62 expression was significantly lower in the COPD group. Based on the results obtained during the present study, it became clear that the inhibition of autophagy could attenuate the ERS-induced apoptosis of AECs in rats with COPD.

Bleomycin-induced apoptosis of alveolar epithelial cells requires angiotensin synthesis de novo

2003 ◽  
Vol 284 (3) ◽  
pp. L501-L507 ◽  
Author(s):  
Xiaopeng Li ◽  
Huiying Zhang ◽  
Valerie Soledad-Conrad ◽  
Jiaju Zhuang ◽  
Bruce D. Uhal
Keyword(s):  
Epithelial Cells ◽  
Caspase 3 ◽  
De Novo ◽  
Enzyme Inhibitor ◽  
Primary Cultures ◽  
A549 Cells ◽  
Cell Loss ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Induced Apoptosis

Primary cultures of rat type II alveolar epithelial cells (AECs) or human AEC-derived A549 cells, when exposed to bleomycin (Bleo), exhibited concentration-dependent apoptosis detected by altered nuclear morphology, fragmentation of DNA, activation of caspase-3, and net cell loss over time. In both cell culture models, exposure to Bleo caused time-dependent increases in angiotensinogen (ANGEN) mRNA. Antisense oligonucleotides against ANGEN mRNA inhibited Bleo-induced apoptosis of rat AEC or A549 cells by 83 and 84%, respectively ( P < 0.01 and P < 0.05), and prevented Bleo-induced net cell loss. Apoptosis of rat AECs or A549 cells in response to Bleo was inhibited 91% by the ANG-converting enzyme inhibitor captopril or 82%, respectively, by neutralizing antibodies specific for ANG II (both P < 0.01). Antagonists of ANG receptor AT1 (losartan, L-158809, or saralasin), but not an AT2-selective blocker (PD-123319), inhibited Bleo-induced apoptosis of either rat AECs (79%, P < 0.01) or A549 cells (83%, P < 0.01) and also reduced the activity of caspase-3 by 52% ( P < 0.05). These data indicate that Bleo, like FasL or TNF-α, induces transactivation of ANG synthesis de novo that is required for AEC apoptosis. They also support the theory that ANG system antagonists have potential for the blockade of AEC apoptosis in situ.

scholarly journals Abrogation of ER stress-induced apoptosis of alveolar epithelial cells by angiotensin 1–7

2013 ◽  
Vol 305 (1) ◽  
pp. L33-L41 ◽  
Author(s):  
Bruce D. Uhal ◽  
Hang Nguyen ◽  
MyTrang Dang ◽  
Indiwari Gopallawa ◽  
Jing Jiang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Er Stress ◽  
Cathepsin D ◽  
Primary Cultures ◽  
A549 Cells ◽  
Surfactant Protein ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Induced Apoptosis ◽  
Jnk Activation

Earlier work showed that apoptosis of alveolar epithelial cells (AECs) in response to endogenous or xenobiotic factors is regulated by autocrine generation of angiotensin (ANG) II and its counterregulatory peptide ANG1–7. Mutations in surfactant protein C (SP-C) induce endoplasmic reticulum (ER) stress and apoptosis in AECs and cause lung fibrosis. This study tested the hypothesis that ER stress-induced apoptosis of AECs might also be regulated by the autocrine ANGII/ANG1–7 system of AECs. ER stress was induced in A549 cells or primary cultures of human AECs with the proteasome inhibitor MG132 or the SP-C BRICHOS domain mutant G100S. ER stress activated the ANGII-generating enzyme cathepsin D and simultaneously decreased the ANGII-degrading enzyme ACE-2, which normally generates the antiapoptotic peptide ANG1–7. TAPI-2, an inhibitor of ADAM17/TACE, significantly reduced both the activation of cathepsin D and the loss of ACE-2. Apoptosis of AECs induced by ER stress was measured by assays of mitochondrial function, JNK activation, caspase activation, and nuclear fragmentation. Apoptosis induced by either MG132 or the SP-C BRICHOS mutant G100S was significantly inhibited by the ANG receptor blocker saralasin and was completely abrogated by ANG1–7. Inhibition by ANG1–7 was blocked by the specific mas antagonist A779. These data show that ER stress-induced apoptosis is mediated by the autocrine ANGII/ANG1–7 system in human AECs and demonstrate effective blockade of SP-C mutation-induced apoptosis by ANG1–7. They also suggest that therapeutic strategies aimed at administering ANG1–7 or stimulating ACE-2 may hold potential for the management of ER stress-induced fibrotic lung disorders.

scholarly journals Photobiomodulation prevents DNA fragmentation of alveolar epithelial cells and alters the mRNA levels of caspase 3 and Bcl-2 genes in acute lung injury

2018 ◽  
Vol 17 (7) ◽  
pp. 975-983 ◽  
Author(s):  
Luiz Philippe da Silva Sergio ◽  
Andrezza Maria Côrtes Thomé ◽  
Larissa Alexsandra da Silva Neto Trajano ◽  
Andre Luiz Mencalha ◽  
Adenilson de Souza da Fonseca ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Alveolar Epithelial Cells ◽  
Mrna Levels ◽  
Alveolar Epithelial ◽  
Life Threatening ◽  
Pulmonary Permeability

Acute lung injury (ALI) is defined as hyperinflammation that could occur from sepsis and lead to pulmonary permeability and edema, making them life-threatening diseases.

scholarly journals Alveolar epithelial cells undergo epithelial-to-mesenchymal transition in response to endoplasmic reticulum stress.

2015 ◽  
Vol 290 (6) ◽  
pp. 3277-3277 ◽  
Author(s):  
Harikrishna Tanjore ◽  
Dong-Sheng Cheng ◽  
Amber L. Degryse ◽  
Donald F. Zoz ◽  
Rasul Abdolrasulnia ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Endoplasmic Reticulum Stress ◽  
Epithelial To Mesenchymal Transition ◽  
Alveolar Epithelial Cells ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial
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