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Am J Physiol Lung Cell Mol Physiol. 2019 Nov 6. doi: 10.1152/ajplung.00123.2019. [Epub ahead of print]

Flavored E-liquids Increase Cytoplasmic Ca2+ Levels in Airway Epithelia.

Author information

1
Cell Biology & Physiology, University of North Carolina at Chapel Hill, United States.
2
University of North Carolina at Chapel Hill.
3
Marsico Lung Institute, UNC, United States.
4
Chemistry, University of North Carolina at Chapel Hill.
5
Signal Transduction Laboratory, NIEHS, United States.

Abstract

E-cigarettes are non-combustible, electronic nicotine delivery devices that aerosolize an e-liquid, i.e. nicotine in a propylene glycol/vegetable glycerin (PG/VG) vehicle that also contains flavors. Whilst the effects of nicotine are relatively well-understood, more information is needed regarding the potential biological effects of the other e-liquid constituents. This is a serious concern, because e-liquids are available in over 7,000 distinct flavors. We have previously demonstrated that many e-liquids affect cell growth/viability through an unknown mechanism. Since Ca2+ is a ubiquitous second messenger that regulates cell growth, we therefore characterized the effects of e-liquids on cellular Ca2+ homeostasis. To better understand the extent of this effect, we screened e-liquids for their ability to alter cytosolic Ca2+ levels and found that 42/100 flavored e-liquids elicited a cellular Ca2+ response. Banana Pudding-flavored e-liquid (Banana Pudding), a representative e-liquid from this group, caused phospholipase C activation, ER Ca2+ release, store-operated Ca2+ entry (SOCE) and protein kinase Cα (PKCα) phosphorylation. However, longer Banana Pudding exposures depleted ER Ca2+ stores and inhibited SOCE, suggesting that Banana Pudding may alter Ca2+ homeostasis by both short- and long-term mechanisms. Since dysregulation of Ca2+ signaling can cause chronic inflammation, ER stress and abnormal cell growth, flavored e-cigarette products that can elicit cell Ca2+ responses should be further screened for potential toxicity.

KEYWORDS:

E-cigarette; Orai1; STIM1; Tobacco; nicotine

PMID:
31693394
DOI:
10.1152/ajplung.00123.2019

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