Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury.
Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury.
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DOI：
10.3390/biom12030393
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发表时间：
2022-03-02
期刊：
影响因子：
5.5
通讯作者：
Wyatt TA
中科院分区：
文献类型：
--
作者：
Ochoa CA;Nissen CG;Mosley DD;Bauer CD;Jordan DL;Bailey KL;Wyatt TA
大多数被诊断患有酒精使用障碍的人吸烟。在同时暴露于香烟烟雾和酒精的肺中发现了高浓度的丙二醛和乙醛。醛类直接损伤肺并形成醛蛋白加合物，影响上皮功能。最近，2-（3-氨基-6-氯喹啉-2-基）丙-2-醇（ADX-102）被开发作为一种捕集药物。我们假设，捕集化合物对香烟烟雾和酒精共同暴露引起的肺损伤具有保护作用。为了检验这一假设，我们用0-100 µM ADX-102预处理小鼠纤毛气管上皮细胞，然后共暴露于5%香烟烟雾提取物和50 mM乙醇。用ADX-102预处理剂量依赖性地保护免受烟雾和酒精诱导的纤毛减慢、支气管上皮细胞伤口修复减少、上皮单层阻力降低和MAA加合物形成。高达100 µM的ADX-102浓度未显示细胞毒性。由于蛋白激酶C（PKC）激活是减缓纤毛和伤口修复的已知机制，因此我们检查了ADX-102对吸烟和酒精诱导的PKC β活性的影响。ADX-102可防止吸烟和饮酒后PKC β的早期（3 h）激活和晚期（24 h）自动下调。这些数据表明，香烟烟雾和酒精代谢产生的活性醛可能是治疗干预以减少肺损伤的潜在靶点。
Most individuals diagnosed with alcohol use disorders smoke cigarettes. Large concentrations of malondialdehyde and acetaldehyde are found in lungs co-exposed to cigarette smoke and alcohol. Aldehydes directly injure lungs and form aldehyde protein adducts, impacting epithelial functions. Recently, 2-(3-Amino-6-chloroquinolin-2-yl)propan-2-ol (ADX-102) was developed as an aldehyde-trapping drug. We hypothesized that aldehyde-trapping compounds are protective against lung injury derived from cigarette smoke and alcohol co-exposure. To test this hypothesis, we pretreated mouse ciliated tracheal epithelial cells with 0–100 µM of ADX-102 followed by co-exposure to 5% cigarette smoke extract and 50 mM of ethanol. Pretreatment with ADX-102 dose-dependently protected against smoke and alcohol induced cilia-slowing, decreases in bronchial epithelial cell wound repair, decreases in epithelial monolayer resistance, and the formation of MAA adducts. ADX-102 concentrations up to 100 µM showed no cellular toxicity. As protein kinase C (PKC) activation is a known mechanism for slowing cilia and wound repair, we examined the effects of ADX-102 on smoke and alcohol induced PKC epsilon activity. ADX-102 prevented early (3 h) activation and late (24 h) autodownregulation of PKC epsilon in response to smoke and alcohol. These data suggest that reactive aldehydes generated from cigarette smoke and alcohol metabolism may be potential targets for therapeutic intervention to reduce lung injury.
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DOI：
10.1016/j.alcohol.2020.10.003
发表时间：
2021-03
期刊：
Alcohol (Fayetteville, N.Y.)
影响因子：
--
作者：
Bailey KL;Samuelson DR;Wyatt TA
通讯作者：
Wyatt TA
DOI：
10.1152/ajplung.1995.268.5.l723
发表时间：
1995-05-01
影响因子：
4.9
作者：
CANTRAL, DE;SISSON, JH;SPURZEM, JR
通讯作者：
SPURZEM, JR
影响因子：
4.4
作者：
Joshi, PC;Applewhite, L;Guidot, DM
通讯作者：
Guidot, DM
影响因子：
16.6
作者：
Schlingmann B;Overgaard CE;Molina SA;Lynn KS;Mitchell LA;Dorsainvil White S;Mattheyses AL;Guidot DM;Capaldo CT;Koval M
通讯作者：
Koval M
影响因子：
2.3
作者：
Berger, John P.;Simet, Samantha M.;Wyatt, Todd A.
通讯作者：
Wyatt, Todd A.