Protective effect of selegiline on cigarette smoke-induced oxidative stress and inflammation in rat lungs in vivo

Cui, Yuting; Liu, Kenneth W. K.; Ip, Mary Sau Man; Liang, Yingmin; Mak, Jcw

doi:10.21037/atm-20-2426

“…Even so, deprenyl significantly reduced BAL levels of cytokine-induced neutrophil chemoattractant, monocyte chemoattractant protein 1 and IL-6 in smoke-treated animals, and increased expression of the anti-inflammatory cytokine IL-10. These changes were associated with reduced phosphorylation of ERK1/2 and p38 MAPKs as well as reduced nuclear translocation of NF-kB p65 subunit in lung tissue extracts (Cui et al, 2020). MAO inhibitor reduction of cytokine expression may in part be explained by a reduction in oxidative stress molecules such as hydrogen peroxide.…”

Section: Mao Inhibitors: Regulation Of Cytokine and Chemokine Expressionmentioning

confidence: 92%

Monoamine Oxidase Inhibitors: A Review of Their Anti-Inflammatory Therapeutic Potential and Mechanisms of Action

Ostadkarampour

¹

,

Putnins

²

2021

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Chronic inflammatory diseases are debilitating, affect patients’ quality of life, and are a significant financial burden on health care. Inflammation is regulated by pro-inflammatory cytokines and chemokines that are expressed by immune and non-immune cells, and their expression is highly controlled, both spatially and temporally. Their dysregulation is a hallmark of chronic inflammatory and autoimmune diseases. Significant evidence supports that monoamine oxidase (MAO) inhibitor drugs have anti-inflammatory effects. MAO inhibitors are principally prescribed for the management of a variety of central nervous system (CNS)-associated diseases such as depression, Alzheimer’s, and Parkinson’s; however, they also have anti-inflammatory effects in the CNS and a variety of non-CNS tissues. To bolster support for their development as anti-inflammatories, it is critical to elucidate their mechanism(s) of action. MAO inhibitors decrease the generation of end products such as hydrogen peroxide, aldehyde, and ammonium. They also inhibit biogenic amine degradation, and this increases cellular and pericellular catecholamines in a variety of immune and some non-immune cells. This decrease in end product metabolites and increase in catecholamines can play a significant role in the anti-inflammatory effects of MAO inhibitors. This review examines MAO inhibitor effects on inflammation in a variety of in vitro and in vivo CNS and non-CNS disease models, as well as their anti-inflammatory mechanism(s) of action.

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“…All cells were stained using cell type-specific mAb. For four months (chronic) exposure, differential cell counts to check the cell influx in neutrophils and macrophages were performed on cytospin slides with Diff-Quick staining (Cui, Liu, Ip, Liang, & Mak, 2020;Lim, Kim, Lee, Bae, & Kim, 2018). The Diff-Quick staining involves sequential dipping of the slides into different solutions -fixative agent (methanol, blue), solution 1 (eosinophilic, orange), and solution 2 (basophilic, blue) followed by rinsing and drying.…”

Section: Differential Cell Count In Bal Fluidmentioning

confidence: 99%

Epithelial Ablation of Miro1/Rhot1 GTPase Leads to Mitochondrial Dysfunction and Lung Inflammation by Cigarette Smoke

Sharma¹,

Wang²,

Muthumalage³

et al. 2021

Preprint

0

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Cigarette smoke (CS) exposure results in lung damage and inflammation through mitochondrial dysfunction. Mitochondria quality control is sustained by Miro1 (Rhot1), a calcium-binding membrane-anchored GTPase by its interaction with PINK1/Parkin during mitophagy. However, the exact mechanism that operates this interaction of mitophagy machinery in Miro1 degradation and CS-induced mitochondrial dysfunction that results in lung inflammation remains unclear. We hypothesized that mitochondrial Miro1 plays an important role in regulating mitophagy machinery and resulting lung inflammation by CS in mouse lung. We showed a role of Miro1 in CS-induced mitochondrial dysfunction and quality control mechanisms. The Rhot1Fl/Fl (WT) and lung epithelial cell-specific Rhot1 KO were exposed to mainstream CS for 3 days (acute) and 4 months (chronic). The cellular infiltration, cytokines, and lung histopathology were studied for the inflammatory response in the lungs. Acute CS exposure showed a notable increase in the total inflammatory cells, macrophages, and neutrophils associated with inflammatory mediators and Miro1 associated mitochondrial quality control proteins Parkin and OPA1. Chronic exposure showed an increase infiltration of total inflammatory cells and neutrophils versus air controls. Histopathological changes, such as pulmonary macrophages and neutrophils were increased in CS exposed mice. The epithelial Miro1 ablation led to augmentation of inflammatory cell infiltration with alteration in the levels of pro-inflammatory cytokines and histopathological changes. Thus, CS induces disruption of mitochondrial quality control mechanisms, and Rhot1/Miro1 mediates the process of CS-induced mitochondrial dysfunction ensuing lung inflammatory responses.

show abstract

“…For four months (chronic) exposure, differential cell counts to check the cell influx in neutrophils and macrophages were performed on cytospin slides with Diff-Quick staining (Cui, Liu, Ip, Liang, & Mak, 2020;Lim, Kim, Lee, Bae, & Kim, 2018). The Diff-Quick staining involves sequential dipping of the slides into different solutions -fixative agent (methanol, blue), solution 1 (eosinophilic, orange), and solution 2 (basophilic, blue) followed by rinsing and 6 drying.…”

Section: Differential Cell Count In Bal Fluidmentioning

confidence: 99%

Epithelial Ablation of Miro1/Rhot1 GTPase Leads to Mitochondrial Dysfunction and Lung Inflammation by Cigarette Smoke

Sharma¹,

Wang²,

Muthumalage³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

Cigarette smoke (CS) exposure results in lung damage and inflammation through mitochondrial dysfunction. Mitochondria quality control is sustained by Miro1 (Rhot1), a calcium-binding membrane-anchored GTPase by its interaction with PINK1/Parkin during mitophagy. However, the exact mechanism that operates this interaction of mitophagy machinery in Miro1 degradation and CS-induced mitochondrial dysfunction that results in lung inflammation remains unclear. We hypothesized that mitochondrial Miro1 plays an important role in regulating mitophagy machinery and resulting lung inflammation by CS in mouse lung. We showed a role of Miro1 in CS-induced mitochondrial dysfunction and quality control mechanisms. The Rhot1Fl/Fl (WT) and lung epithelial cell-specific Rhot1 KO were exposed to mainstream CS for 3 days (acute) and 4 months (chronic). The cellular infiltration, cytokines, and lung histopathology were studied for the inflammatory response in the lungs. Acute CS exposure showed a notable increase in the total inflammatory cells, macrophages, and neutrophils associated with inflammatory mediators and Miro1 associated mitochondrial quality control proteins Parkin and OPA1. Chronic exposure showed an increase infiltration of total inflammatory cells and neutrophils versus air controls. Histopathological changes, such as pulmonary macrophages and neutrophils were increased in CS exposed mice. The epithelial Miro1 ablation led to augmentation of inflammatory cell infiltration with alteration in the levels of pro-inflammatory cytokines and histopathological changes. Thus, CS induces disruption of mitochondrial quality control mechanisms, and Rhot1/Miro1 mediates the process of CS-induced mitochondrial dysfunction ensuing lung inflammatory responses.

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Protective effect of selegiline on cigarette smoke-induced oxidative stress and inflammation in rat lungs in vivo

Cited by 23 publications

References 59 publications

Monoamine Oxidase Inhibitors: A Review of Their Anti-Inflammatory Therapeutic Potential and Mechanisms of Action

Monoamine Oxidase Inhibitors: A Review of Their Anti-Inflammatory Therapeutic Potential and Mechanisms of Action

Epithelial Ablation of Miro1/Rhot1 GTPase Leads to Mitochondrial Dysfunction and Lung Inflammation by Cigarette Smoke

Epithelial Ablation of Miro1/Rhot1 GTPase Leads to Mitochondrial Dysfunction and Lung Inflammation by Cigarette Smoke

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