Nicotinic Acetylcholine Receptors Are Sensors For Ethanol In Lung Fibroblasts

Ritzenthaler, Jeffrey D.; Guidot, David M.; Roman-Rodriguez, Jesse

doi:10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1263

Cited by 5 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have demonstrated that ARDS occurs 3.7 times more frequently in people meeting the diagnostic criteria for alcohol-use disorders (Moss, Bucher, Moore, Moore, & Parsons, 1996; Ritzenthaler, Roser-Page, Guidot, & Roman, 2013). Excessive alcohol exposure can damage target organs via mechanisms including inflammation, oxidative stress, and/or tissue remodeling.…”

Section: Alcohol and The Lungmentioning

confidence: 99%

Alcohol and inflammatory responses: Highlights of the 2015 Alcohol and Immunology Research Interest Group (AIRIG) meeting

Cannon

Morris

Hammer

et al. 2016

Alcohol

View full text Add to dashboard Cite

On September 27, 2015 the 20th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite symposium at the annual meeting of the Society for Leukocyte Biology in Raleigh, NC. The 2015 meeting focused broadly on adverse effects of alcohol and alcohol-use disorders in multiple organ systems. Divided into two plenary sessions, AIRIG opened with the topic of pulmonary inflammation as a result of alcohol consumption, which was followed by alcohol’s effect on multiple organs, including the brain and liver. With presentations showing the diverse range of underlying pathology and mechanisms associated with multiple organs as a result of alcohol consumption, AIRIG emphasized the importance of continued alcohol research, as its detrimental consequences are not limited to one or even two organs, but rather extend to the entire host as a whole.

show abstract

Section: Alcohol and The Lungmentioning

confidence: 99%

Alcohol and inflammatory responses: Highlights of the 2015 Alcohol and Immunology Research Interest Group (AIRIG) meeting

Cannon

Morris

Hammer

et al. 2016

Alcohol

View full text Add to dashboard Cite

show abstract

“…Previously, we showed that α4 nicotinic acetylcholine receptors (α4 nAChRs) act as alcohol sensors in mouse lung fibroblasts. Both pharmacological inhibitors and down‐regulation of α4 nAChR by siRNA inhibited the alcohol‐induced expression of fibronectin in these cells (Ritzenthaler et al, 2013; Roman et al, 2005). These nAChRs are members of a family of nonselective cation channels that are activated by the neurotransmitter acetylcholine and are widely expressed at synaptic junctions (Lindstrom, 1997; Lindstrom et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Mice lacking α4 nicotinic acetylcholine receptors are protected against alcohol‐associated liver injury

Watson

Ritzenthaler

Torres-González

et al. 2022

Alcoholism Clin & Exp Res

Self Cite

View full text Add to dashboard Cite

Background: Chronic heavy alcohol consumption is a major risk factor for the development of liver steatosis, fibrosis, and cirrhosis, but the mechanisms by which alcohol causes liver damage remain incompletely elucidated. This group has reported that α4 nicotinic acetylcholine receptors (α4 nAChRs) act as sensors for alcohol in lung cells.This study tested the hypothesis that α4 nAChRs mediate the effects of alcohol in the liver.Methods: Expression of acetylcholine receptor subunits in mouse liver was determined by RNA sequencing (RNA-seq). α4 nAChR knockout (α4 KO) mice were generated in C57BL/6J mice by introducing a mutation encoding an early stop codon in exon 4 of Chrna4, the gene encoding the α4 subunit of the nAChR. The presence of the inactivating mutation was established by polymerase chain reaction and genomic sequencing, and the lack of α4 nAChR function was confirmed in primary fibroblasts isolated from the α4 KO mice. Wild-type (WT) and α4 KO mice were fed the Lieber-DeCarli diet (with 36% of calories from alcohol) or pair fed an isocaloric maltose-dextrin control diet for a 6-week period that included a ramping up phase of increasing dietary alcohol.Results: Chrna4 was the most abundantly expressed nAChR subunit gene in mouse livers. After 6 weeks of alcohol exposure, WT mice had elevated serum transaminases and their livers showed increased fat accumulation, decreased Sirt1 protein levels, and accumulation of markers of oxidative stress and inflammation including Cyp2E1, Nos2, Sod1, Slc7a11, TNFα, and PAI1. All these responses to alcohol were either absent or significantly attenuated in α4 KO animals. Conclusion:Together, these observations support the conclusion that activation of α4 nAChRs by alcohol or one of its metabolites is one of the initial events promoting the accumulation of excess fat and expression of inflammatory mediators. Thus, α4 nAChRs may represent viable targets for intervention in chronic alcohol-related liver disease.

show abstract

“…A further area of focus would be to determine the effect of oxidative stress on nicotinic acetylcholine receptor activation. We have published findings that a modification of two cysteines in the α4 subunit within the α4 nAChR inhibits alcohol-induced cellular modifications [85]. Anti-oxidants and oxidants, N-acetylcysteine, paraquat, H 2 O 2 , and nicotine will be used on cells in vitro with modified cysteine "knock ins" being developed for the α subunits in the α7 nAChR to test possible activation mechanisms.…”

Section: α7 Nachr Activation By Oxidative Stressmentioning

confidence: 99%

The role of a7 nicotine acetylcholine receptors in lung injury and repair.

Vicary¹

View full text Add to dashboard Cite

Nicotinic Acetylcholine Receptors Are Sensors For Ethanol In Lung Fibroblasts

Cited by 5 publications

References 32 publications

Alcohol and inflammatory responses: Highlights of the 2015 Alcohol and Immunology Research Interest Group (AIRIG) meeting

Alcohol and inflammatory responses: Highlights of the 2015 Alcohol and Immunology Research Interest Group (AIRIG) meeting

Mice lacking α4 nicotinic acetylcholine receptors are protected against alcohol‐associated liver injury

The role of a7 nicotine acetylcholine receptors in lung injury and repair.

Contact Info

Product

Resources

About