Dataset Information

Airway Exposure to E-Cigarette Vapors Impairs Autophagy and Induces Aggresome Formation.

ABSTRACT:

Aims

Electronic cigarettes (e-cigarettes) are proposed to be a safer alternative to tobacco cigarettes. Hence, we evaluated if e-cigarette vapors (eCV) impair cellular proteostasis similar to cigarette smoke exposure.

Results

First, we evaluated the impact of eCV exposure (2.5 or 7.5 mg) on Beas2b cells that showed significant increase in accumulation of total polyubiquitinated proteins (Ub, insoluble fractions) with time-dependent decrease in proteasomal activities from 1 h (p < 0.05), 3 h (p < 0.001) to 6 h (p < 0.001) of eCV exposure compared to room air control. We verified that even minimal eCV exposure (1 h) induces valosin-containing protein (VCP; p < 0.001), sequestosome-1/p62 (aberrant autophagy marker; p < 0.05), and aggresome formation (total poly-Ub-accumulation; p < 0.001) using immunoblotting (IB), fluorescence microscopy, and immunoprecipitation (IP). The inhibition of protein synthesis by 6 h of cycloheximide (50 μg/ml) treatment significantly (p < 0.01) alleviates eCV-induced (1 h) aggresome bodies. We also observed that eCV (1 h)-induced protein aggregation can activate oxidative stress, apoptosis (caspase-3/7), and senescence (p < 0.01) compared to room air controls. We verified using an autophagy inducer carbamazepine (20 μM, 6 h) or cysteamine (250 μM; 6 h, antioxidant) that eCV-induced changes in oxidative stress, poly-ub-accumulation, proteasomal activity, autophagy, apoptosis, and/or senescence could be controlled by autophagy induction. We further confirmed the role of acute eCV exposure on autophagy impairment in murine lungs (C57BL/6 and CD1) by IB (Ub, p62, VCP) and IP (VCP, p62), similar to in-vitro experiments.

Innovation

In this study, we report for the first time that eCV exposure induces proteostasis/autophagy impairment leading to oxidative stress, apoptosis, and senescence that can be ameliorated by an autophagy inducer.

Conclusion

eCV-induced autophagy impairment and aggresome formation suggest their potential role in chronic obstructive pulmonary disease-emphysema pathogenesis. Antioxid. Redox Signal. 00, 000-000.

SUBMITTER: Shivalingappa PC

PROVIDER: S-EPMC4744882 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Airway Exposure to E-Cigarette Vapors Impairs Autophagy and Induces Aggresome Formation.

Shivalingappa Prashanth Chandramani PC Hole Rachel R Westphal Colin Van CV Vij Neeraj N

Antioxidants & redox signaling 20151027 4

<h4>Aims</h4>Electronic cigarettes (e-cigarettes) are proposed to be a safer alternative to tobacco cigarettes. Hence, we evaluated if e-cigarette vapors (eCV) impair cellular proteostasis similar to cigarette smoke exposure.<h4>Results</h4>First, we evaluated the impact of eCV exposure (2.5 or 7.5 mg) on Beas2b cells that showed significant increase in accumulation of total polyubiquitinated proteins (Ub, insoluble fractions) with time-dependent decrease in proteasomal activities from 1 h (p < ...[more]

PMID: 26377848

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Project description:Background: Particulate matter (PM) air pollution causes deleterious health effects; however, less is known about health effects of indoor air particulate matter (IAP). Objective: To understand whether IAP influences distinct mechanisms in the development of respiratory tract infections, including bacterial growth, biofilm formation, and innate immunity. Additionally, we tested whether IAP from Iowa houses of subjects with and without recent respiratory exacerbations recapitulated the National Institute of Standards and Technology (NIST) IAP findings. Methods: To test the effect of NIST and Iowa IAP on bacterial growth and biofilm formation, we assessed Staphylococcus aureus growth and Pseudomonas aeruginosa biofilm formation with and without the presence of IAP. To assess the effect of IAP on innate immunity, we exposed primary human airway surface liquid (ASL) to NIST, and Iowa IAP. Lastly, we tested whether specific metals may be responsible for effects on airway innate immunity. Results: NIST and Iowa IAP significantly enhanced bacterial growth and biofilm formation. NIST IAP (whole particle and the soluble portion) impaired ASL antimicrobial activity. IAP from one Iowa home significantly impaired ASL antimicrobial activity (p < 0.05), and five other homes demonstrated a trend (p ≤ 0.18) of impaired ASL antimicrobial activity. IAP from homes of subjects with a recent history of respiratory exacerbation tended (p = 0.09) to impair ASL antimicrobial activity more than IAP from homes of those without a history respiratory exacerbation. Aluminum and Magnesium impaired ASL antimicrobial activity, while copper was bactericidal. Combining metals varied their effect on ASL antimicrobial activity. Conclusions: NIST IAP and Iowa IAP enhanced bacterial growth and biofilm formation. ASL antimicrobial activity was impaired by NIST IAP, and Iowa house IAP from subjects with recent respiratory exacerbation tended to impair ASL antimicrobial activity. Individual metals may explain impaired ASL antimicrobial activity; however, antimicrobial activity in the presence of multiple metals warrants further study.

Dataset Information

Airway Exposure to E-Cigarette Vapors Impairs Autophagy and Induces Aggresome Formation.

Aims

Results

Innovation

Conclusion

Publications

Airway Exposure to E-Cigarette Vapors Impairs Autophagy and Induces Aggresome Formation.

Similar Datasets

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