Identification of stable cytotoxic factors in the gas phase extract of cigarette smoke and pharmacological characterization of their cytotoxicity

Noya, Yoichi; Seki, Koh‐ichi; Asano, Hiroshi; Mai, Yosuke; Horinouchi, Takahiro; Higashi, Taishi; Terada, Koji; Hatate, Chizuru; Hoshi, Akimasa; Nepal, Prabha; Horiguchi, Michiko; Kuge, Yuji; Miwa, Soichi

doi:10.1016/j.tox.2013.08.015

Cited by 43 publications

(52 citation statements)

References 41 publications

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“…As expected, the cytotoxic effects of CSE, ACR, and MVK are prevented by a PKC inhibitor, bisindolylmaleimide I. 6,8,9) These results indicate that Ca 2+ -dependent activation of PKCα is required for the cell damage induced by CSE, ACR, and MVK. There is accumulating evidence that other PKC isozymes also play important roles in the cellular responses to cigarette smoke.…”

Section: Involvement Of Protein Kinase C-depen-dent Activation Of Nadsupporting

confidence: 77%

“…Nicotine-and tar-free CSE induces translocation of PKCα from cytosol to the plasma membrane as well as plasma membrane damage and cell apoptosis, all of which are inhibited by chelating intracellular Ca 2+ but not extracellular Ca 2+ . 9) Both ACR and MVK also cause plasma membrane damage, 6) cell apoptosis, 6) and translocation of PKCα to the plasma membrane (unpublished data). As expected, the cytotoxic effects of CSE, ACR, and MVK are prevented by a PKC inhibitor, bisindolylmaleimide I.…”

Section: Involvement Of Protein Kinase C-depen-dent Activation Of Nadmentioning

confidence: 92%

“…6) With respect to the impact of carbonyl compounds present in the gas phase on human health, we focus on the cytotoxic effects of CSE, ACR, and MVK, and their mechanisms.…”

Section: )mentioning

confidence: 99%

“…5,6,8,9) PKC is a family of serine/threonine kinases that regulate a multitude of cellular processes, including proliferation, differentiation, apoptosis, inflammation, and migration. 20,21) The PKC family comprises ten distinct isozymes that can be divided into three subfamilies such as conventional PKC isozymes (α, βI, βII, and γ), novel PKC isozymes (δ, ε, η, and θ), and atypical PKC isozymes (ζ and ι/λ), based on their structural properties and co-factor requirements for activation (see review by Igumenova).…”

Section: Involvement Of Protein Kinase C-depen-dent Activation Of Nadmentioning

confidence: 99%

“…4) Thus the tar phase and gas phase are defined as material that is trapped on the filter and that passes through the filter, respectively. [4][5][6] To characterize the pharmacological properties of the gas phase of cigarette smoke, several studies have employed nicotine-and tar-free cigarette smoke extract (CSE), which is prepared by bubbling cigarette mainstream smoke in aqueous solution such as phosphatebuffered saline after passage through the Cambridge filter.…”

Section: Introductionmentioning

confidence: 99%

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Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties

Horinouchi

Higashi

Mazaki

et al. 2016

Biological & Pharmaceutical Bulletin

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Cigarette mainstream smoke is composed of gas and tar phases and contains >4000 chemical constituents, including nicotine and tar. The substances in the gas phase but not in the tar phase can pass through the airway epithelial barrier, enter the systemic circulation via the pulmonary circulation, and increase systemic oxidative damage, leading to the development of cigarette smoking-related diseases such as atherosclerosis. Recently, we identified some stable carbonyl compounds, including acrolein (ACR) and methyl vinyl ketone (MVK), as major cytotoxic factors in nicotine-and tar-free cigarette smoke extract (CSE) of the gas phase. CSE, ACR, and MVK induce protein kinase C (PKC)-dependent activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and subsequent generation of reactive oxygen species (ROS) via NOX, causing plasma membrane damage and cell apoptosis. CSE, ACR, and MVK also trigger carbonylation of PKC, which is an irreversible oxidative modification. Cell damage and PKC carbonylation in response to treatment with CSE, ACR, or MVK are abolished by thiol-containing antioxidants such as N-acetyl-L-cysteine and reduced glutathione. Thus pharmacological modulation of PKC and NOX activities and the trapping of ROS are potential strategies for the prevention of diseases related to cigarette smoking.

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Section: Involvement Of Protein Kinase C-depen-dent Activation Of Nadsupporting

confidence: 77%

Section: Involvement Of Protein Kinase C-depen-dent Activation Of Nadmentioning

confidence: 92%

“…6) With respect to the impact of carbonyl compounds present in the gas phase on human health, we focus on the cytotoxic effects of CSE, ACR, and MVK, and their mechanisms.…”

Section: )mentioning

confidence: 99%

Section: Involvement Of Protein Kinase C-depen-dent Activation Of Nadmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties

Horinouchi

Higashi

Mazaki

et al. 2016

Biological & Pharmaceutical Bulletin

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Acrolein and Unsaturated Aldehydes

Bein¹,

Leikauf²

2020

Environmental Toxicants

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Collecting e‐cigarette aerosols for in vitro applications: A survey of the biomedical literature and opportunities to increase the value of submerged cell culture‐based assessments

Smart

Phillips

2020

J of Applied Toxicology

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Electronic nicotine delivery systems (ENDS) are being developed as potentially reduced-risk alternatives to the continued use of combustible tobacco products. Because of the widespread uptake of ENDS-in particular, e-cigarettes-the biological effects, including the toxic potential, of their aerosols are under investigation. Preclinically, collection of such aerosols is a prerequisite for testing in submerged cell culture-based in vitro assays; however, despite the growth in this research area, there is no apparent standardized collection method for this application. To this end, through an Institute for in vitro Sciences, Inc. workshop initiative, we surveyed the biomedical literature catalogued in PubMed® to map the types of methods hitherto used and reported publicly. From the 47 relevant publications retrieved, we identified seven distinct collection methods. Bubble-through (with aqueous solvents) and Cambridge filter pad (CFP) (with polar solvents) collection were the most frequently cited methods (57% and 18%, respectively), while the five others (CFP + bubble-through; condensation; cotton filters; settle-upon; settle-upon + dry) were cited less often (2-10%). Critically, the collected aerosol fractions were generally found to be only minimally characterized chemically, if at all. Furthermore, there was large heterogeneity among other experimental parameters (e.g., vaping regimen). Consequently, we recommend that more comprehensive research be conducted to identify the method(s) that produce the fraction(s) most representative of the native aerosol. We also endorse standardization of the aerosol generation process. These should be regarded as opportunities for increasing the value of in vitro assessments in relation to predicting effects on human health. K E Y W O R D S aerosol collection, e-cigarette, in vitro assays, literature survey, submerged cell cultures 1 | INTRODUCTION Electronic nicotine delivery systems (ENDS) are being developed as potentially reduced-risk alternatives to the continued use of combustible tobacco products (Brandon et al., 2015; Farsalinos & Polosa, 2014). Electronic cigarettes (e-cigarettes)-one of the most widely known ENDS-consist of a battery-powered device that heats an "e-liquid" contained inside an atomizer, which leads to generation

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Identification of stable cytotoxic factors in the gas phase extract of cigarette smoke and pharmacological characterization of their cytotoxicity

Cited by 43 publications

References 41 publications

Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties

Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties

Acrolein and Unsaturated Aldehydes

Collecting e‐cigarette aerosols for in vitro applications: A survey of the biomedical literature and opportunities to increase the value of submerged cell culture‐based assessments

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