ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Inhibition of protein phosphatase 1 reverses alcohol-induced ciliary dysfunction.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Alcohol's Effects on the Lung and Lung Disease.Alcohol research : current reviews · 2025Pooled it
- Article
- Defining minimum media requirements forPeerJ · 2026Article
- Assessment of liquid media requirements for storing and evaluating respiratory cilia motility.PeerJ · 2025Article
- Reduction of Alcohol-Dependent Lung Pathological Features in Rats Treated with Fenofibrate.International journal of molecular sciences · 2024Article
- Mucociliary Wnt signaling promotes cilia biogenesis and beating.Nature communications · 2023Article
- Pharmacological reversal of post-transcriptional alterations implicated in alcohol-induced alveolar macrophage dysfunction.Alcohol (Fayetteville, N.Y.) · 2023Article
- Activated Protein Phosphatase 2A Disrupts Nutrient Sensing Balance Between Mechanistic Target of Rapamycin Complex 1 and Adenosine Monophosphate-Activated Protein Kinase, Causing Sarcopenia in Alcohol-Associated Liver Disease.Hepatology (Baltimore, Md.) · 2021Article
- Motile cilia genetics and cell biology: big results from little mice.Cellular and molecular life sciences : CMLS · 2021Review
- Effect of nicotinamide riboside on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice.Food science & nutrition · 2021Article
- Loss of cAMP-dependent stimulation of isolated cilia motility by alcohol exposure is oxidant-dependent.Alcohol (Fayetteville, N.Y.) · 2019Article
- Redox regulation of motile cilia in airway disease.Redox biology · 2019Review
- PKA, PP1, and DC1 phosphorylation mediate alcohol-induced ciliary dysfunction in Chlamydomonas reinhardtii.Alcohol (Fayetteville, N.Y.) · 2019Article
- The reduced activity of PP-1α under redox stress condition is a consequence of GSH-mediated transient disulfide formation.Scientific reports · 2018Article
- S-nitrosation of protein phosphatase 1 mediates alcohol-induced ciliary dysfunction.Scientific reports · 2018Article
- Ccdc181 is a microtubule-binding protein that interacts with Hook1 in haploid male germ cells and localizes to the sperm tail and motile cilia.European journal of cell biology · 2017Article
- Alcohol drivesAmerican journal of physiology. Lung cellular and molecular physiology · 2017Article
- Alcohol and lung injury and immunity.Alcohol (Fayetteville, N.Y.) · 2016Review
- Chronic Ethanol Exposure: Pathogenesis of Pulmonary Disease and Dysfunction.Biomolecules · 2015Review
- Cyclic GMP and Cilia Motility.Cells · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Airway mucociliary clearance is a first-line defense of the lung against inhaled particles and debris. Among individuals with alcohol use disorders, there is an increase in lung diseases. We previously identified that prolonged alcohol exposure impairs mucociliary clearance, known as alcohol-induced ciliary dysfunction (AICD). Cilia-localized enzymes, known as the ciliary metabolon, are key to the pathogenesis of AICD. In AICD, cyclic nucleotide-dependent ciliary kinases, which modulate phosphorylation to regulate cilia beat, are desensitized. We hypothesized that alcohol activates cilia-associated protein phosphatase 1 (PP1) activity, driving phosphorylation changes of cilia motility regulatory proteins. To test this hypothesis we identified the effects of prolonged alcohol exposure on phosphatase activity, cilia beat, and kinase responsiveness and cilia-associated phosphorylation targets when stimulated by β-agonist or cAMP. Prolonged alcohol activated PP1 and blocked cAMP-dependent cilia beat and protein kinase A (PKA) responsiveness and phosphorylation of a 29-kDa substrate of PKA. Importantly, prolonged alcohol-induced phosphatase activation was inhibited by the PP1 specific inhibitor, inhibitor-2 (I-2), restoring cAMP-stimulated cilia beat and PKA responsiveness and phosphorylation of the 29-kDa substrate. The I-2 inhibitory effect persisted in tissue, cell, and isolated cilia-organelle models, highlighting the association of ciliary metabolon-localized enzymes to AICD. Prolonged alcohol exposure drives ciliary metabolon-localized PP1 activation. PP1 activation modifies phosphorylation of a 29-kDa protein related to PKA activity. These data reinforce our previous findings that alcohol is acting at the level of the ciliary metabolon to cause ciliary dysfunction and identifies PP1 as a therapeutic target to prevent or reverse AICD.
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