Autophagy and pulmonary disease

The autophagic pathway involves the encapsulation of substrates in double-membraned vesicles, which are subsequently delivered to the lysosome for enzymatic degradation and recycling of metabolic precursors. Autophagy is a major cellular defense against oxidative stress, or related conditions that cause accumulation of damaged proteins or organelles. Selective forms of autophagy can maintain organelle populations or remove aggregated proteins. Dysregulation of redox homeostasis under pathological conditions results in excessive generation of reactive oxygen species (ROS), leading to oxidative stress and the associated oxidative damage of cellular components. Accumulating evidence indicates that autophagy is necessary to maintain redox homeostasis. ROS activates autophagy, which facilitates cellular adaptation and diminishes oxidative damage by degrading and recycling intracellular damaged macromolecules and dysfunctional organelles. The cellular responses triggered by oxidative stress include the altered regulation of signaling pathways that culminate in the regulation of autophagy. Current research suggests a central role for autophagy as a mammalian oxidative stress response and its interrelationship to other stress defense systems. Altered autophagy phenotypes have been observed in lung diseases such as chronic obstructive lung disease, acute lung injury, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension, and asthma. Understanding the mechanisms by which ROS regulate autophagy will provide novel therapeutic targets for lung diseases. This review highlights our current understanding on the interplay between ROS and autophagy in the development of pulmonary disease.

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“…A growing body of evidence supports an important role of autophagy in idiopathic pulmonary fibrosis ( ) [ [290] , [291] , [292] ] ( Fig. 4 ).…”

Section: Autophagy and Ros In Pulmonary Diseasesmentioning

confidence: 99%

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

et al. 2020

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“…MSCs might alleviate LPS-ALI via downregulation of miR-142a-5p that permits pulmonary epithelial cells (PECs) to proceed with Beclin 1-mediated cell autophagy [ 127 ]. In lung disease, the bacterial studies demonstrated that the penetration of Acinetobacter baumannii activated the ubiquitin-mediated autophagic response that depends on the septins SEPT2 and SEPT9 and it is due to the Beclin 1-dependent AMPK/ERK/mTOR pathway [ 128 ].…”

Section: Lung Injury: Clinical Implicationsmentioning

confidence: 99%

Autophagy markers as mediators of lung injury-implication for therapeutic intervention

Vishnupriya¹,

Dharshini²,

Sakthivel

et al. 2020

Life Sciences

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Lung injury is characterized by inflammatory processes demonstrated as loss of function of the pulmonary capillary endothelial and alveolar epithelial cells. Autophagy is an intracellular digestion system that work as an inducible adaptive response to lung injury which is a resultant of exposure to various stress agents like hypoxia, ischemia-reperfusion and xenobiotics which may be manifested as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic lung injury (CLI), bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), asthma, ventilator-induced lung injury (VILI), ventilator-associated lung injury (VALI), pulmonary fibrosis (PF), cystic fibrosis (CF) and radiation-induced lung injury (RILI). Numerous regulators like LC3B-II, Beclin 1, p62, HIF1/BNIP3 and mTOR play pivotal role in autophagy induction during lung injury possibly for progression/inhibition of the disease state. The present review focuses on the critical autophagic mediators and their potential cross talk with the lung injury pathophysiology thereby bringing to limelight the possible therapeutic interventions.

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“…For example, Xue et al (17) demonstrated that apoptosis stimulating protein of p53 promotes tumor growth by increasing autophagic flux in human non-small cell lung cancer, whereas HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) acts as a tumor suppressor by ubiquitinating optineurin (OPTN) and activating selective autophagy (18). Autophagy is also involved in lung cancer therapy, chemotherapy induces tumor cell autophagy, and inhibiting autophagy enhances the sensitivity of lung cancer cells to chemotherapy (19).…”

Section: Introductionmentioning

confidence: 99%

Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549 cells

Yang

Zhao

et al. 2020

Oncol Lett

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Propofol (2,6-diisopropylphenol) is one of the most commonly used intravenous anesthetics and possesses a number of non-anesthetic effects, including antitumor function. The aim of the present study was to elucidate the antitumor molecular mechanism of propofol on A549 and H1299 cells. A549 and H1299 cells were treated in the presence or absence of different concentrations (0, 60 or 120 µmol) of propofol for different durations (0, 24, 48 or 72 h), and proliferation was detected by MTT and colony formation assays; the protein levels of optineurin (OPTN) ubiquitination, HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), methyl-CpG binding domain protein 3 (MBD3) and Microtubule-associated protein 1A/1B-light chain 3 were detected by immunoblotting or quantitative (q)PCR; the methylation state of the HACE1 gene promoter was detected by bisulfite DNA sequencing; and binding of MBD3 on HACE1 gene promoter was detected by chromatin immunoprecipitation-qPCR. Propofol inhibited proliferation of A549 and H1299 cells and promoted HACE1-OPTN axis-mediated selective autophagy activity by increasing the protein expression levels of HACE1 via demethylating its promoter region. Furthermore, propofol promoted expression levels of MBD3 and binding to the-1,000 to-1 bp (transcription start site) region of HACE1 gene promoter. MBD3-knockdown experiments indicated that propofol inhibited proliferation of A549 cells in a MBD3-dependent manner. Thus, the findings of the present study provided a potential antitumor molecular mechanism mediated by propofol.

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Autophagy and pulmonary disease

Cited by 63 publications

References 93 publications

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

Autophagy markers as mediators of lung injury-implication for therapeutic intervention

Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549 cells

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Autophagy and pulmonary disease

Cited by 63 publications

References 93 publications

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

Autophagy markers as mediators of lung injury-implication for therapeutic intervention

Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549&nbsp;cells

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Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549 cells