scholarly journals Sirtuin 1 Promotes Hyperoxia-Induced Lung Epithelial Cell Death Independent of NF-E2–Related Factor 2 Activation

2016 ◽  
Vol 54 (5) ◽  
pp. 697-706 ◽  
Author(s):  
Haranatha R. Potteti ◽  
Subbiah Rajasekaran ◽  
Senthilkumar B. Rajamohan ◽  
Chandramohan R. Tamatam ◽  
Narsa M. Reddy ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Epithelial Cell ◽  
Sirtuin 1 ◽  
Related Factor ◽  
Lung Epithelial ◽  
Epithelial Cell Death

scholarly journals The NRF2 Activation and Antioxidative Response Are Not Impaired Overall during Hyperoxia-Induced Lung Epithelial Cell Death

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Haranatha R. Potteti ◽  
Narsa M. Reddy ◽  
Tom K. Hei ◽  
Dhananjaya V. Kalvakolanu ◽  
Sekhar P. Reddy
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Epithelial Cell ◽  
Airway Epithelial Cells ◽  
Lung Epithelial Cell ◽  
Nuclear Accumulation ◽  
Related Factor ◽  
Nrf2 Activation ◽  
Lung Epithelial ◽  
Epithelial Cell Death

Lung epithelial and endothelial cell death caused by pro-oxidant insults is a cardinal feature of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients. The NF-E2-related factor 2 (NRF2) activation in response to oxidant exposure is crucial to the induction of several antioxidative and cytoprotective enzymes that mitigate cellular stress. Since prolonged exposure to hyperoxia causes cell death, we hypothesized that chronic hyperoxia impairs NRF2 activation, resulting in cell death. To test this hypothesis, we exposed nonmalignant small airway epithelial cells (AECs) to acute (1–12 h) and chronic (36–48 h) hyperoxia and evaluated cell death, NRF2 nuclear accumulation and target gene expression, and NRF2 recruitment to the endogenousHMOX1andNQO1promoters. As expected, hyperoxia gradually induced death in AECs, noticeably and significantly by 36 h; ~60% of cells were dead by 48 h. However, we unexpectedly found increased expression levels of NRF2-regulated antioxidative genes and nuclear NRF2 in AECs exposed to chronic hyperoxia as compared to acute hyperoxia. Chromatin Immunoprecipitation (ChIP) assays revealed an increased recruitment of NRF2 to the endogenousHMOX1andNQO1promoters in AECs exposed to acute or chronic hyperoxia. Thus, our findings demonstrate that NRF2 activation and antioxidant gene expression are functional during hyperoxia-induced lung epithelial cell death and that chronic hyperoxia does not impair NRF2 signaling overall.

scholarly journals NLRP3 deletion protects from hyperoxia-induced acute lung injury

2013 ◽  
Vol 305 (2) ◽  
pp. C182-C189 ◽  
Author(s):  
Jutaro Fukumoto ◽  
Itsuko Fukumoto ◽  
Prasanna Tamarapu Parthasarathy ◽  
Ruan Cox ◽  
Bao Huynh ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Epithelial Cell ◽  
Inflammasome Activation ◽  
Nlrp3 Gene ◽  
Lung Epithelial ◽  
Epithelial Cell Death

Inspiration of a high concentration of oxygen, a therapy for acute lung injury (ALI), could unexpectedly lead to reactive oxygen species (ROS) production and hyperoxia-induced acute lung injury (HALI). Nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) senses the ROS, triggering inflammasome activation and interleukin-1β (IL-1β) production and secretion. However, the role of NLRP3 inflammasome in HALI is unclear. The main aim of this study is to determine the effect of NLRP3 gene deletion on inflammatory response and lung epithelial cell death. Wild-type (WT) and NLRP3−/− mice were exposed to 100% O2 for 48–72 h. Bronchoalveolar lavage fluid and lung tissues were examined for proinflammatory cytokine production and lung inflammation. Hyperoxia-induced lung pathological score was suppressed in NLRP3−/− mice compared with WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1β, TNFα, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 were attenuated in NLRP3−/− mice. NLRP3 deletion decreased lung epithelial cell death and caspase-3 levels and a suppressed NF-κB levels compared with WT controls. Taken together, this research demonstrates for the first time that NLRP3-deficient mice have suppressed inflammatory response and blunted lung epithelial cell apoptosis to HALI.

scholarly journals TRIM72 mediates lung epithelial cell death upon hyperoxia exposure

2020 ◽  
Vol 84 (1) ◽  
pp. 79-86
Author(s):  
Liang-Ti Huang ◽  
Hsiu-Chu Chou ◽  
Chung-Ming Chen
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Epithelial Cell ◽  
Lung Epithelial ◽  
Hyperoxia Exposure ◽  
Epithelial Cell Death

Protective effect of polaprezinc on cadmium-induced injury of lung epithelium

Metallomics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1310-1320 ◽  
Author(s):  
Kazuma Kimura ◽  
Yukari Nakano ◽  
Toshifumi Sugizaki ◽  
Mikako Shimoda ◽  
Nahoko Kobayashi ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Protective Effect ◽  
Lung Epithelial Cell ◽  
Lung Epithelium ◽  
Lung Epithelial ◽  
Epithelial Cell Death

The induction of metallothioneins by polaprezinc contributes to its protective effect against cadmium-induced lung epithelial cell death.

scholarly journals Platelets inhibit apoptotic lung epithelial cell death and protect mice against infection-induced lung injury

2019 ◽  
Vol 3 (3) ◽  
pp. 432-445 ◽  
Author(s):  
William Bain ◽  
Tolani Olonisakin ◽  
Minting Yu ◽  
Yanyan Qu ◽  
Mei Hulver ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Lung Epithelial Cell ◽  
Barrier Disruption ◽  
Lung Epithelial ◽  
Epithelial Cell Death ◽  
Alveolar Capillary

Abstract Thrombocytopenia is associated with worse outcomes in patients with acute respiratory distress syndrome, which is most commonly caused by infection and marked by alveolar–capillary barrier disruption. However, the mechanisms by which platelets protect the lung alveolar–capillary barrier during infectious injury remain unclear. We found that natively thrombocytopenic Mpl−/− mice deficient in the thrombopoietin receptor sustain severe lung injury marked by alveolar barrier disruption and hemorrhagic pneumonia with early mortality following acute intrapulmonary Pseudomonas aeruginosa (PA) infection; barrier disruption was attenuated by platelet reconstitution. Although PA infection was associated with a brisk neutrophil influx, depletion of airspace neutrophils failed to substantially mitigate PA-triggered alveolar barrier disruption in Mpl−/− mice. Rather, PA cell-free supernatant was sufficient to induce lung epithelial cell apoptosis in vitro and in vivo and alveolar barrier disruption in both platelet-depleted mice and Mpl−/− mice in vivo. Cell-free supernatant from PA with genetic deletion of the type 2 secretion system, but not the type 3 secretion system, mitigated lung epithelial cell death in vitro and lung injury in Mpl−/− mice. Moreover, platelet releasates reduced poly (ADP ribose) polymerase cleavage and lung injury in Mpl−/− mice, and boiling of platelet releasates, but not apyrase treatment, abrogated PA supernatant–induced lung epithelial cell cytotoxicity in vitro. These findings indicate that while neutrophil airspace influx does not potentiate infectious lung injury in the thrombocytopenic host, platelets and their factors protect against severe pulmonary complications from pathogen-secreted virulence factors that promote host cell death even in the absence of overt infection.

Sign in / Sign up

Export Citation Format

Share Document