醛脱氢酶 3A1 可保护气道上皮细胞免受香烟烟雾诱导的 DNA 损伤和细胞毒性。
Aldehyde dehydrogenase 3A1 protects airway epithelial cells from cigarette smoke-induced DNA damage and cytotoxicity.
机构信息
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA; New Mexico VA Health Care System, Albuquerque, NM 87108, USA; COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
出版信息
Free Radic Biol Med. 2014 Mar;68:80-6. doi: 10.1016/j.freeradbiomed.2013.11.028. Epub 2013 Dec 4.
Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS). Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA levels showed the greatest induction in response to CS extract (CSE) exposure of primary human bronchial epithelial cells (HBECs). ALDH3A1 protein accumulation was accompanied by increased ALDH enzymatic activity in CSE-exposed immortalized HBECs. The effects of overexpression or suppression of ALDH3A1 on CSE-induced cytotoxicity and DNA damage (γH2AX) were evaluated in cultured immortalized HBECs. Enforced expression of ALDH3A1 attenuated cytotoxicity and downregulated γH2AX. SiRNA-mediated suppression of ALDH3A1 blocked ALDH enzymatic activity and augmented cytotoxicity in CSE-exposed cells. Our results suggest that the availability of ALDH3A1 is important for cell survival against CSE in HBECs.
乙醛脱氢酶 3A1（ALDH3A1）是 ALDH 超家族的成员，能够催化活性醛的氧化，而活性醛是香烟烟雾（CS）中的高毒性成分。即便如此，ALDH3A1 在 CS 诱导的细胞毒性和 DNA 损伤中的作用尚未得到检验。在所有的 ALDH 超家族成员中，ALDH3A1 mRNA 水平在原代人支气管上皮细胞（HBEC）暴露于 CS 提取物（CSE）时表现出最大程度的诱导。在暴露于 CSE 的永生化 HBEC 中，ALDH3A1 蛋白积累伴随着 ALDH 酶活性的增加。在培养的永生化 HBEC 中，评估了过表达或抑制 ALDH3A1 对 CSE 诱导的细胞毒性和 DNA 损伤（γH2AX）的影响。ALDH3A1 的强制表达减轻了细胞毒性并下调了 γH2AX。用 siRNA 介导的 ALDH3A1 抑制阻断了 CSE 暴露细胞中的 ALDH 酶活性并增强了细胞毒性。我们的研究结果表明，ALDH3A1 的可用性对于 HBEC 中的细胞在 CSE 下的存活很重要。
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