scholarly journals Hydrogen Sulfide Attenuates Hydrogen Peroxide-Induced Injury in Human Lung Epithelial A549 Cells

2019 ◽  
Vol 20 (16) ◽  
pp. 3975 ◽  
Author(s):  
Mingqi Wang ◽  
Xinyu Cao ◽  
Chang Luan ◽  
Zhengqiang Li
Keyword(s):  
Hydrogen Peroxide ◽  
Hydrogen Sulfide ◽  
Lung Injury ◽  
Er Stress ◽  
Human Lung ◽  
A549 Cells ◽  
Mapk Signaling ◽  
Protective Mechanism ◽  
Lung Epithelial ◽  
Pre Treatment

Lung tissues are frequently exposed to a hyperoxia environment, which leads to oxidative stress injuries. Hydrogen sulfide (H2S) is widely implicated in physiological and pathological processes and its antioxidant effect has attracted much attention. Therefore, in this study, we used hydrogen peroxide (H2O2) as an oxidative damage model to investigate the protective mechanism of H2S in lung injury. Cell death induced by H2O2 treatment could be significantly attenuated by the pre-treatment of H2S, resulting in a decrease in the Bax/Bcl-2 ratio and the inhibition of caspase-3 activity in human lung epithelial cell line A549 cells. Additionally, the results showed that H2S decreased reactive oxygen species (ROS), as well as neutralized the damaging effects of H2O2 in mitochondria energy-producing and cell metabolism. Pre-treatment of H2S also decreased H2O2-induced suppression of endogenous H2S production enzymes, cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE), and 3-mercapto-pyruvate sulfurtransferase (MPST). Furthermore, the administration of H2S attenuated [Ca2+] overload and endoplasmic reticulum (ER) stress through the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, H2S might be a potential therapeutic agent for reducing ROS and ER stress-associated apoptosis against H2O2-induced lung injury.

Ionizing radiation enhances matrix metalloproteinase-2 production in human lung epithelial cells

2001 ◽  
Vol 280 (1) ◽  
pp. L30-L38 ◽  
Author(s):  
Jun Araya ◽  
Muneharu Maruyama ◽  
Kazuhiko Sassa ◽  
Tadashi Fujita ◽  
Ryuji Hayashi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ionizing Radiation ◽  
Basement Membrane ◽  
Lung Injury ◽  
Human Lung ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Radiation Induced ◽  
Human Lung Epithelial Cells

Radiation pneumonitis is a major complication of radiation therapy. However, the detailed cellular mechanisms have not been clearly defined. Based on the recognition that basement membrane disruption occurs in acute lung injury and that matrix metalloproteinase (MMP)-2 can degrade type IV collagen, one of the major components of the basement membrane, we hypothesized that ionizing radiation would modulate MMP-2 production in human lung epithelial cells. To evaluate this, the modulation of MMP-2 with irradiation was investigated in normal human bronchial epithelial cells as well as in A549 cells. We measured the activity of MMP-2 in the conditioned medium with zymography and the MMP-2 mRNA level with RT-PCR. Both of these cells constitutively expressed 72-kDa gelatinolytic activity, corresponding to MMP-2, and exposure to radiation increased this activity. Consistent with the data of zymography, ionizing radiation increased the level of MMP-2 mRNA. This radiation-induced increase in MMP-2 expression was mediated via p53 because the p53 antisense oligonucleotide abolished the increase in MMP-2 activity as well as the accumulation of p53 after irradiation in A549 cells. These results indicate that MMP-2 expression by human lung epithelial cells is involved in radiation-induced lung injury.

scholarly journals Hydrogen Peroxide Causes Cell Death via Increased Transcription of HOXB13 in Human Lung Epithelial A549 Cells

Toxics ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 78
Author(s):  
Naoki Endo ◽  
Takashi Toyama ◽  
Akira Naganuma ◽  
Yoshiro Saito ◽  
Gi-Wook Hwang
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Human Lung ◽  
A549 Cells ◽  
Protein Levels ◽  
Intracellular Ros ◽  
Lung Epithelial ◽  
Homeobox Protein

Although homeobox protein B13 (HOXB13) is an oncogenic transcription factor, its role in stress response has rarely been examined. We previously reported that knockdown of HOXB13 reduces the cytotoxicity caused by various oxidative stress inducers. Here, we studied the role of HOXB13 in cytotoxicity caused by hydrogen peroxide in human lung epithelial A549 cells. The knockdown of HOXB13 reduced hydrogen peroxide-induced cytotoxicity; however, this phenomenon was largely absent in the presence of antioxidants (Trolox or N-acetyl cysteine (NAC)). This suggests that HOXB13 may be involved in the cytotoxicity caused by hydrogen peroxide via the production of reactive oxygen species (ROS). Hydrogen peroxide also increased both the mRNA and protein levels of HOXB13. However, these increases were rarely observed in the presence of a transcriptional inhibitor, which suggests that hydrogen peroxide increases protein levels via increased transcription of HOXB13. Furthermore, cell death occurred in A549 cells that highly expressed HOXB13. However, this cell death was mostly inhibited by treatment with antioxidants. Taken together, our findings indicate that HOXB13 may be a novel factor involved in the induction of oxidative stress, which causes cell death via intracellular ROS production.

scholarly journals Histone Deacetylases Promote ER Stress Induced Epithelial Mesenchymal Transition in Human Lung Epithelial Cells

2018 ◽  
Vol 46 (5) ◽  
pp. 1821-1834 ◽  
Author(s):  
Daishun Liu ◽  
Honglan Zhu ◽  
Ling Gong ◽  
Shenglan Pu ◽  
Yang Wu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Er Stress ◽  
Histone Deacetylases ◽  
Human Lung ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Smad Pathway ◽  
Mesenchymal Transition ◽  
Lung Epithelial

Background/Aims: Epithelial to mesenchymal transition (EMT) is a crucial process involved in pulmonary fibrosis. This study aimed to explore the role of histone deacetylases (HDACs) and endoplasmic reticulum (ER) stress in EMT in human lung epithelial cells. Methods: Human lung adenocarcinoma A549 cells were treated with bleomycin and tunicamycin to induce EMT. The proliferation of A549 cells was detected by MTT assay. The expression of HDACs and EMT markers was detected by PCR and Western blot analysis. The secretion of TGF-β1 and collagen I was examined by ELISA. Results: A549 cells switched from a cobblestone-like appearance to an elongated fibroblast like appearance after exposure to tunicamycin or bleomycin, accompanied by increased expression of N-cadherin, α-SMA and Collagen I. Meanwhile, GRP78 was upregulated in A549 cells exposed to tunicamycin or bleomycin. These changes induced by tunicamycin or bleomycin could be abrogated by 4-PBA. Moreover, tunicamycin and bleomycin promoted the expression of HDAC2 and HDAC6, and HDACs inhibitor SAHA abrogated the morphological and biochemical changes in A549 cells. 4-PBA and SAHA inhibited the upregulation of pulmonary fibrosis factors TGF-β1 and IL-32 and the activation of Smad pathway induced by tunicamycin or bleomycin. Conclusions: We provide the first evidence that tunicamycin and bleomycin induce ER stress and EMT in lung epithelial cells via the upregulation of HDACs. HDACs inhibitor could inhibit ER stress induced upregulation of pulmonary fibrosis factors and the activation of Smad pathway. HDACs inhibitors are promising agents for the therapy of pulmonary fibrosis.

scholarly journals Matrine Attenuates COX-2 and ICAM-1 Expressions in Human Lung Epithelial Cells and Prevents Acute Lung Injury in LPS-Induced Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Chian-Jiun Liou ◽  
You-Rong Lai ◽  
Ya-Ling Chen ◽  
Yi-Hsien Chang ◽  
Zih-Ying Li ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Human Lung ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Intercellular Adhesion Molecule ◽  
Lung Epithelial ◽  
Cox 2 ◽  
Human Lung Epithelial Cells

Matrine is isolated from Sophora flavescens and shows anti-inflammatory effects in macrophages. Here we evaluated matrine’s suppressive effects on cyclooxygenase 2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) expressions in lipopolysaccharide- (LPS-) stimulated human lung epithelial A549 cells. Additionally, BALB/c mice were given various matrine doses by intraperitoneal injection, and then lung injury was induced via intratracheal instillation of LPS. In LPS-stimulated A549 cells, matrine inhibited the productions of interleukin-8 (IL-8), monocyte chemotactic protein-1, and IL-6 and decreased COX-2 expression. Matrine treatment also decreased ICAM-1 protein expression and suppressed the adhesion of neutrophil-like cells to inflammatory A549 cells. In vitro results demonstrated that matrine significantly inhibited mitogen-activated protein kinase phosphorylation and decreased nuclear transcription factor kappa-B subunit p65 protein translocation into the nucleus. In vivo data indicated that matrine significantly inhibited neutrophil infiltration and suppressed productions of tumor necrosis factor-α and IL-6 in mouse bronchoalveolar lavage fluid and serum. Analysis of lung tissue showed that matrine decreased the gene expression of proinflammatory cytokines, chemokines, COX-2, and ICAM-1. Our findings suggest that matrine improved lung injury in mice and decreased the inflammatory response in human lung epithelial cells.

scholarly journals Polyhexamethylene Guanidine Phosphate Induces Apoptosis through Endoplasmic Reticulum Stress in Lung Epithelial Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1215
Author(s):  
Mi Ho Jeong ◽  
Mi Seon Jeon ◽  
Ga Eun Kim ◽  
Ha Ryong Kim
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Epithelial Cell ◽  
Er Stress ◽  
Lung Fibrosis ◽  
A549 Cells ◽  
Polyhexamethylene Guanidine ◽  
Lung Epithelial ◽  
Epithelial Cell Death ◽  
Guanidine Phosphate

Airway epithelial cell death contributes to the pathogenesis of lung fibrosis. Polyhexamethylene guanidine phosphate (PHMG-p), commonly used as a disinfectant, has been shown to be strongly associated with lung fibrosis in epidemiological and toxicological studies. However, the molecular mechanism underlying PHMG-p-induced epithelial cell death is currently unclear. We synthesized a PHMG-p–fluorescein isothiocyanate (FITC) conjugate and assessed its uptake into lung epithelial A549 cells. To examine intracellular localization, the cells were treated with PHMG-p–FITC; then, the cytoplasmic organelles were counterstained and observed with confocal microscopy. Additionally, the organelle-specific cell death pathway was investigated in cells treated with PHMG-p. PHMG-p–FITC co-localized with the endoplasmic reticulum (ER), and PHMG-p induced ER stress in A549 cells and mice. The ER stress inhibitor tauroursodeoxycholic acid (TUDCA) was used as a pre-treatment to verify the role of ER stress in PHMG-p-induced cytotoxicity. The cells treated with PHMG-p showed apoptosis, which was inhibited by TUDCA. Our results indicate that PHMG-p is rapidly located in the ER and causes ER-stress-mediated apoptosis, which is an initial step in PHMG-p-induced lung fibrosis.

scholarly journals EGCG promotes PRKCA expression to alleviate LPS-induced acute lung injury and inflammatory response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mian Wang ◽  
Hua Zhong ◽  
Xian Zhang ◽  
Xin Huang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Weight Ratio ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Protective Mechanism ◽  
High Morbidity ◽  
Inflammatory Factor ◽  
Egcg Treatment

AbstractAcute lung injury (ALI), which could be induced by multiple factors such as lipopolysaccharide (LPS), refer to clinical symptoms of acute respiratory failure, commonly with high morbidity and mortality. Reportedly, active ingredients from green tea have anti-inflammatory and anticancer properties, including epigallocatechin-3-gallate (EGCG). In the present study, protein kinase C alpha (PRKCA) is involved in EGCG protection against LPS-induced inflammation and ALI. EGCG treatment attenuated LPS-stimulated ALI in mice as manifested as improved lung injury scores, decreased total cell amounts, neutrophil amounts and macrophage amounts, inhibited the activity of MPO, decreased wet-to-dry weight ratio of lung tissues, and inhibited release of inflammatory cytokines TNF-α, IL-1β, and IL-6. PRKCA mRNA and protein expression showed to be dramatically decreased by LPS treatment while reversed by EGCG treatment. Within LPS-stimulated ALI mice, PRKCA silencing further aggravated, while PRKCA overexpression attenuated LPS-stimulated inflammation and ALI through MAPK signaling pathway. PRKCA silencing attenuated EGCG protection. Within LPS-induced RAW 264.7 macrophages, EGCG could induce PRKCA expression. Single EGCG treatment or Lv-PRKCA infection attenuated LPS-induced increases in inflammatory factors; PRKCA silencing could reverse the suppressive effects of EGCG upon LPS-stimulated inflammatory factor release. In conclusion, EGCG pretreatment inhibits LPS-induced ALI in mice. The protective mechanism might be associated with the inhibitory effects of PRKCA on proinflammatory cytokine release via macrophages and MAPK signaling pathway.

scholarly journals Comparative Toxic Effects of Manufactured Nanoparticles and Atmospheric Particulate Matter in Human Lung Epithelial Cells

2020 ◽  
Vol 18 (1) ◽  
pp. 22
Author(s):  
Yun Wu ◽  
Mei Wang ◽  
Shaojuan Luo ◽  
Yunfeng Gu ◽  
Dongyang Nie ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Human Lung ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Atmospheric Particulate Matter ◽  
Toxic Effects ◽  
Ros Generation ◽  
Atmospheric Particulate ◽  
Significant Difference ◽  
Lung Epithelial

Although nanoparticles (NPs) have been used as simplified atmospheric particulate matter (PM) models, little experimental evidence is available to support such simulations. In this study, we comparatively assessed the toxic effects of PM and typical NPs (four carbonaceous NPs with different morphologies, metal NPs of Fe, Al, and Ti, as well as SiO2 NPs) on human lung epithelial A549 cells. The EC50 value of PM evaluated by cell viability assay was 148.7 μg/mL, closest to that of SiO2 NPs, between the values of carbonaceous NPs and metal NPs. All particles caused varying degrees of reactive oxygen species (ROS) generation and adenosine triphosphate (ATP) suppression. TiO2 NPs showed similar performance with PM in inducing ROS production (p < 0.05). Small variations between two carbonaceous NPs (graphene oxides and graphenes) and PM were also observed at 50 μg/mL. Similarly, there was no significant difference in ATP inhibition between carbonaceous NPs and PM, while markedly different effects were caused by SiO2 NP and TiO2 NP exposure. Our results indicated that carbonaceous NPs could be served as potential surrogates for urban PM. The identification of PM model may help us further explore the specific roles and mechanisms of various components in PM.

Enhancing Effect of Poly(amino acid)s on Albumin Uptake in Human Lung Epithelial A549 Cells

2013 ◽  
Vol 28 (6) ◽  
pp. 497-503 ◽  
Author(s):  
Ryoko Yumoto ◽  
Sayuri Suzuka ◽  
Saori Nishimoto ◽  
Junya Nagai ◽  
Mikihisa Takano
Keyword(s):  
Amino Acid ◽  
Human Lung ◽  
A549 Cells ◽  
Enhancing Effect ◽  
Lung Epithelial

Bioactive extracts of Ziziphus mauritiana induces apoptosis in A549 human lung epithelial carcinoma cells through the generation of reactive oxygen species

2021 ◽  
Vol 17 ◽  
Author(s):  
Om Prakash ◽  
Shazia Usmani ◽  
Amresh Gupta ◽  
Asif Jafri ◽  
Mohammad Fahad Ullah ◽  
...  
Keyword(s):  
Mtt Assay ◽  
Human Lung ◽  
A549 Cells ◽  
Carcinoma Cells ◽  
Ziziphus Mauritiana ◽  
Meoh Extract ◽  
Lung Carcinomas ◽  
Pharmacological Significance ◽  
Lung Epithelial ◽  
A549 Lung

Background: In recent years, novel metabolites isolated from botanical sources have attracted much attention for traditional and therapeutic significance. The ethnopharmacological studies suggest that Ziziphus mauritiana is a common remedy against several kinds of ailments. Objective: The current study has evaluated the MeOH extract of Ziziphus mauritiana leaves (ZME) through physicochemical, phytochemical, and chromatographic fingerprinting analysis, which displayed an array of biometabolites of pharmacological significance including flavonoids. Methods: The extract was further examined for anticancer activities which revealed promising anticancer properties against human lung epithelial carcinoma cells (A549) and induction of apoptosis impart by ROS. The oxidative stress was evaluated in terms of production and accumulation of cytosolic extent of ROS whereas anticancer perspective was determined by MTT assay, cell morphology analysis, followed by nuclear condensation for the examination of apoptosis induction. Results: Finding suggests that the MeOH extract of ZME markedly exhibited promising anticancer activity against the A549 lung epithelial carcinoma cell. The ZME was found to be most active in the MTT assay against A549 cells while it was less toxic to normal cells. The intracellular ROS generation was remarkably induced by ZME, which correlated with the ability of the flavonoid-rich fractions in the MeOH extract to inhibit cell growth and might induce apoptosis. Conclusion: The present study provides useful insight concerning the promising anticancer potential of ZME against A549 lung carcinomas. However, the clinical correlation will be required for its authorization and in the discovery of significant and least noxious novel agents against lung carcinomas.

Sign in / Sign up

Export Citation Format

Share Document