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

Abstract

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.

Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

“…The oxidative stress associated with increases in reactive oxygen species (ROS) is interconnected with autophagy [ 56 , 57 ]. Oxidative stress leads to oxidative damage of proteins, lipids, and nucleic acids.…”

“…Intermittent activation of Nrf2 through the canonical pathway confers cellular protection and functional integrity whereas prolonged activation of Nrf2 through the noncanonical pathway appears to be detrimental, resulting in tissue injuries and inflammation [ 49 ]. In acute lung injury, autophagy is induced by different stimuli including the oxidative stress [ 57 ]. However, the role of autophagy in acute lung injury still remains controversial depending on the underlying cause of the lung injury, on the cell types, and on the stage of lung injury.…”

The Role of Heat Shock Protein 70 kDa in Asthma

“…98 Activation of autophagy is also involved in the NET formation (that implication in asthma was described above) and in neutrophilic airway inflammation. 65,96 Thus, the facts above indicate that intracellular HSP70 contribute to ER stress-induced UPR, UPS, and autophagy. All these processes are observed in asthma, particularly severe asthma.…”

“…97,98 Single nucleotide polymorphisms in autophagy-related gene Atg5 are associated with reduced lung function and airway remodeling. 93,96 Also, the expression of Atg5 product was higher in lung tissue samples of asthma patients compared with nonasthmatic samples. 97 Furthermore, in the ovalbumin-induced mouse model of asthma, the treatment with Atg5 short hairpin RNA inhibited autophagy together with asthma features such as airway hyperreactivity and eosinophilia.…”

“…95 In certain conditions, carbon nanoparticles can trigger or exacerbate airway inflammation in asthma, and chaperon-mediated autophagy can be potentially involved in inflammation regulation. 95,96 The role of autophagy in asthma is widely discussed and thought to be associated with airway remodeling and severe asthma. 97,98 Single nucleotide polymorphisms in autophagy-related gene Atg5 are associated with reduced lung function and airway remodeling.…”