Alcohol drives S-nitrosylation and redox activation of protein phosphatase 1, causing bovine airway cilia dysfunction

Michael E. Price, Jacqueline A. Pavlik, Miao Liu, Shi Jian Ding, Todd A Wyatt, Joseph Harold Sisson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Individuals with alcohol (ethanol)-use disorders are at increased risk for lung infections, in part, due to defective mucociliary clearance driven by motile cilia in the airways. We recently reported that isolated, demembranated bovine cilia (axonemes) are capable of producing nitric oxide (·NO) when exposed to biologically relevant concentrations of alcohol. This increased presence of ·NO can lead to protein S-nitrosylation, a posttranslational modification signaling mechanism involving reversible adduction of nitrosonium cations or ·NO to thiolate or thiyl radicals, respectively, of proteins forming S-nitrosothiols (SNOs). We quantified and compared SNO content between isolated, demembranated axonemes extracted from bovine tracheae, with or without in situ alcohol exposure (100 mM = 24 h). We demonstrate that relevant concentrations of alcohol exposure shift the S-nitrosylation status of key cilia regulatory proteins, including 20-fold increases in S-nitrosylation of proteins that include protein phosphatase 1 (PP1). With the use of an ATP-reactivated axoneme motility system, we demonstrate that alcohol-driven S-nitrosylation of PP1 is associated with PP1 activation and dysfunction of axoneme motility. These new data demonstrate that alcohol can shift the S-nitrothiol balance at the level of the cilia organelle and highlight S-nitrosylation as a novel signaling mechanism to regulate PP1 and cilia motility.

Original languageEnglish (US)
Pages (from-to)L432-L439
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume312
Issue number3
DOIs
StatePublished - Mar 10 2017

Fingerprint

Protein Phosphatase 1
Cilia
Axoneme
Oxidation-Reduction
Alcohols
Protein S
S-Nitrosothiols
Nitric Oxide
Mucociliary Clearance
Post Translational Protein Processing
Trachea
Organelles
Cations
Ethanol
Adenosine Triphosphate
Lung
Infection
Proteins

Keywords

  • Alcohol
  • Cilia
  • Redox regulation
  • S-nitrosylation

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology (medical)

Cite this

Alcohol drives S-nitrosylation and redox activation of protein phosphatase 1, causing bovine airway cilia dysfunction. / Price, Michael E.; Pavlik, Jacqueline A.; Liu, Miao; Ding, Shi Jian; Wyatt, Todd A; Sisson, Joseph Harold.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 312, No. 3, 10.03.2017, p. L432-L439.

Research output: Contribution to journalArticle

@article{793df18d97204134952222f75e614d96,
title = "Alcohol drives S-nitrosylation and redox activation of protein phosphatase 1, causing bovine airway cilia dysfunction",
abstract = "Individuals with alcohol (ethanol)-use disorders are at increased risk for lung infections, in part, due to defective mucociliary clearance driven by motile cilia in the airways. We recently reported that isolated, demembranated bovine cilia (axonemes) are capable of producing nitric oxide (·NO) when exposed to biologically relevant concentrations of alcohol. This increased presence of ·NO can lead to protein S-nitrosylation, a posttranslational modification signaling mechanism involving reversible adduction of nitrosonium cations or ·NO to thiolate or thiyl radicals, respectively, of proteins forming S-nitrosothiols (SNOs). We quantified and compared SNO content between isolated, demembranated axonemes extracted from bovine tracheae, with or without in situ alcohol exposure (100 mM = 24 h). We demonstrate that relevant concentrations of alcohol exposure shift the S-nitrosylation status of key cilia regulatory proteins, including 20-fold increases in S-nitrosylation of proteins that include protein phosphatase 1 (PP1). With the use of an ATP-reactivated axoneme motility system, we demonstrate that alcohol-driven S-nitrosylation of PP1 is associated with PP1 activation and dysfunction of axoneme motility. These new data demonstrate that alcohol can shift the S-nitrothiol balance at the level of the cilia organelle and highlight S-nitrosylation as a novel signaling mechanism to regulate PP1 and cilia motility.",
keywords = "Alcohol, Cilia, Redox regulation, S-nitrosylation",
author = "Price, {Michael E.} and Pavlik, {Jacqueline A.} and Miao Liu and Ding, {Shi Jian} and Wyatt, {Todd A} and Sisson, {Joseph Harold}",
year = "2017",
month = "3",
day = "10",
doi = "10.1152/ajplung.00513.2016",
language = "English (US)",
volume = "312",
pages = "L432--L439",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Alcohol drives S-nitrosylation and redox activation of protein phosphatase 1, causing bovine airway cilia dysfunction

AU - Price, Michael E.

AU - Pavlik, Jacqueline A.

AU - Liu, Miao

AU - Ding, Shi Jian

AU - Wyatt, Todd A

AU - Sisson, Joseph Harold

PY - 2017/3/10

Y1 - 2017/3/10

N2 - Individuals with alcohol (ethanol)-use disorders are at increased risk for lung infections, in part, due to defective mucociliary clearance driven by motile cilia in the airways. We recently reported that isolated, demembranated bovine cilia (axonemes) are capable of producing nitric oxide (·NO) when exposed to biologically relevant concentrations of alcohol. This increased presence of ·NO can lead to protein S-nitrosylation, a posttranslational modification signaling mechanism involving reversible adduction of nitrosonium cations or ·NO to thiolate or thiyl radicals, respectively, of proteins forming S-nitrosothiols (SNOs). We quantified and compared SNO content between isolated, demembranated axonemes extracted from bovine tracheae, with or without in situ alcohol exposure (100 mM = 24 h). We demonstrate that relevant concentrations of alcohol exposure shift the S-nitrosylation status of key cilia regulatory proteins, including 20-fold increases in S-nitrosylation of proteins that include protein phosphatase 1 (PP1). With the use of an ATP-reactivated axoneme motility system, we demonstrate that alcohol-driven S-nitrosylation of PP1 is associated with PP1 activation and dysfunction of axoneme motility. These new data demonstrate that alcohol can shift the S-nitrothiol balance at the level of the cilia organelle and highlight S-nitrosylation as a novel signaling mechanism to regulate PP1 and cilia motility.

AB - Individuals with alcohol (ethanol)-use disorders are at increased risk for lung infections, in part, due to defective mucociliary clearance driven by motile cilia in the airways. We recently reported that isolated, demembranated bovine cilia (axonemes) are capable of producing nitric oxide (·NO) when exposed to biologically relevant concentrations of alcohol. This increased presence of ·NO can lead to protein S-nitrosylation, a posttranslational modification signaling mechanism involving reversible adduction of nitrosonium cations or ·NO to thiolate or thiyl radicals, respectively, of proteins forming S-nitrosothiols (SNOs). We quantified and compared SNO content between isolated, demembranated axonemes extracted from bovine tracheae, with or without in situ alcohol exposure (100 mM = 24 h). We demonstrate that relevant concentrations of alcohol exposure shift the S-nitrosylation status of key cilia regulatory proteins, including 20-fold increases in S-nitrosylation of proteins that include protein phosphatase 1 (PP1). With the use of an ATP-reactivated axoneme motility system, we demonstrate that alcohol-driven S-nitrosylation of PP1 is associated with PP1 activation and dysfunction of axoneme motility. These new data demonstrate that alcohol can shift the S-nitrothiol balance at the level of the cilia organelle and highlight S-nitrosylation as a novel signaling mechanism to regulate PP1 and cilia motility.

KW - Alcohol

KW - Cilia

KW - Redox regulation

KW - S-nitrosylation

UR - http://www.scopus.com/inward/record.url?scp=85015153476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85015153476&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00513.2016

DO - 10.1152/ajplung.00513.2016

M3 - Article

VL - 312

SP - L432-L439

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 3

ER -