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Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties
| Title: | Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties |
| Authors: | Horinouchi, Takahiro Browse this author →KAKEN DB | | Higashi, Tsunehito Browse this author →KAKEN DB | | Mazaki, Yuichi Browse this author | | Miwa, Soichi Browse this author →KAKEN DB |
| Keywords: | cigarette smoke extract (CSE) | | acrolein (ACR) | | methyl vinyl ketone (MVK) | | protein kinase C (PKC) | | reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) | | protein carbonylation |
| Issue Date: | Jun-2016 |
| Publisher: | The Pharmaceutical Society of Japan |
| Journal Title: | Biological and pharmaceutical bulletin |
| Volume: | 39 |
| Issue: | 6 |
| Start Page: | 909 |
| End Page: | 914 |
| Publisher DOI: | 10.1248/bpb.b16-00025 |
| PMID: | 27251492 |
| Abstract: | 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/62431 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 堀之内 孝広
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