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
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DOI：
10.1248/bpb.b16-00025
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发表时间：
2016-06-01
影响因子：
2
通讯作者：
Miwa, Soichi
中科院分区：
文献类型：
--
作者：
Horinouchi, Takahiro;Higashi, Tsunehito;Miwa, Soichi
卷烟主流烟气由气相和焦油相组成，含有超过 4000 种化学成分，包括尼古丁和焦油。气相而非焦油相的物质可以穿过气道上皮屏障，经肺循环进入体循环，增加全身氧化损伤，导致动脉粥样硬化等吸烟相关疾病的发生。最近，我们发现一些稳定的羰基化合物，包括丙烯醛（ACR）和甲基乙烯基酮（MVK），是气相无尼古丁和无焦油卷烟烟雾提取物（CSE）中的主要细胞毒性因子。 CSE、ACR 和 MVK 诱导蛋白激酶 C (PKC) 依赖性的还原型烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 氧化酶 (NOX) 激活，并随后通过 NOX 生成活性氧 (ROS)，导致质膜损伤和细胞凋亡。 CSE、ACR 和 MVK 也会引发 PKC 的羰基化，这是一种不可逆的氧化修饰。 CSE、ACR 或 MVK 治疗引起的细胞损伤和 PKC 羰基化可被含硫醇的抗氧化剂（例如 N-乙酰基-L-半胱氨酸和还原型谷胱甘肽）消除。因此，PKC 和 NOX 活性的药理学调节以及 ROS 的捕获是预防与吸烟相关的疾病的潜在策略。
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.