Extracellular Release of Mitochondrial DNA: Triggered by Cigarette Smoke and Detected in COPD.
Extracellular Release of Mitochondrial DNA: Triggered by Cigarette Smoke and Detected in COPD.
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DOI：
10.3390/cells11030369
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发表时间：
2022-01-22
期刊：
影响因子：
6
通讯作者：
Kaufman BA
中科院分区：
文献类型：
--
作者：
Giordano L;Gregory AD;Pérez Verdaguer M;Ware SA;Harvey H;DeVallance E;Brzoska T;Sundd P;Zhang Y;Sciurba FC;Shapiro SD;Kaufman BA
吸烟（CS）是慢性阻塞性肺疾病（COPD）最常见的危险因素。本研究的目的是阐明是否在CS暴露后释放mtDNA，并在受COPD影响的前吸烟者的血浆中检测到mtDNA，这可能是气道损伤的结果。我们检测了慢性阻塞性肺疾病患者血浆和CS诱导的肺气肿小鼠血清中的游离线粒体DNA（cf-mtDNA）和核DNA（cf-nDNA）。慢性阻塞性肺疾病患者血浆和CS诱发肺气肿小鼠血清cf-mtDNA水平升高。在细胞培养中，暴露于亚致死剂量的CSE降低了线粒体膜电位，增加了氧化应激，线粒体动力学失调，并触发了细胞外囊泡（EV）中的mtDNA释放。线粒体DNA释放到EV中伴随着与DNA损伤反应相关的标志物的表达增加，包括DNA酶III、DNA敏感受体（cGAS和NLRP 3）、促炎细胞因子（IL-1β、IL-6、IL-8、IL-18和CXCL 2）和衰老标志物（p16和p21）;大多数反应也是由体外细胞溶质DNA递送触发的。暴露于致死剂量的CSE优先诱导细胞碎片中的mtDNA和nDNA释放。总的来说，本研究的结果将线粒体应激、炎症和衰老的标志物与CSE暴露诱导的mtDNA释放相关联。由于在COPD患者血浆和肺气肿小鼠血清中检测到高cf-mtDNA，我们的研究结果支持未来研究cf-mtDNA作为响应CS暴露和COPD病理的线粒体应激的标志物。
Cigarette smoke (CS) is the most common risk factor for chronic obstructive pulmonary disease (COPD). The present study aimed to elucidate whether mtDNA is released upon CS exposure and is detected in the plasma of former smokers affected by COPD as a possible consequence of airway damage. We measured cell-free mtDNA (cf-mtDNA) and nuclear DNA (cf-nDNA) in COPD patient plasma and mouse serum with CS-induced emphysema. The plasma of patients with COPD and serum of mice with CS-induced emphysema showed increased cf-mtDNA levels. In cell culture, exposure to a sublethal dose of CSE decreased mitochondrial membrane potential, increased oxidative stress, dysregulated mitochondrial dynamics, and triggered mtDNA release in extracellular vesicles (EVs). Mitochondrial DNA release into EVs occurred concomitantly with increased expression of markers that associate with DNA damage responses, including DNase III, DNA-sensing receptors (cGAS and NLRP3), proinflammatory cytokines (IL-1β, IL-6, IL-8, IL-18, and CXCL2), and markers of senescence (p16 and p21); the majority of the responses are also triggered by cytosolic DNA delivery in vitro. Exposure to a lethal CSE dose preferentially induced mtDNA and nDNA release in the cell debris. Collectively, the results of this study associate markers of mitochondrial stress, inflammation, and senescence with mtDNA release induced by CSE exposure. Because high cf-mtDNA is detected in the plasma of COPD patients and serum of mice with emphysema, our findings support the future study of cf-mtDNA as a marker of mitochondrial stress in response to CS exposure and COPD pathology.
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影响因子：
82.9
作者：
Cloonan SM;Glass K;Laucho-Contreras ME;Bhashyam AR;Cervo M;Pabón MA;Konrad C;Polverino F;Siempos II;Perez E;Mizumura K;Ghosh MC;Parameswaran H;Williams NC;Rooney KT;Chen ZH;Goldklang MP;Yuan GC;Moore SC;Demeo DL;Rouault TA;D'Armiento JM;Schon EA;Manfredi G;Quackenbush J;Mahmood A;Silverman EK;Owen CA;Choi AM
通讯作者：
Choi AM
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.2147/copd.s113256
发表时间：
2016
影响因子：
2.8
作者：
Avriel A;Rozenberg D;Raviv Y;Heimer D;Bar-Shai A;Gavish R;Sheynin J;Douvdevani A
通讯作者：
Douvdevani A
影响因子：
4.6
作者：
King PT;Sharma R;O'Sullivan KM;Callaghan J;Dousha L;Thomas B;Ruwanpura S;Lim S;Farmer MW;Jennings BR;Finsterbusch M;Brooks G;Selemidis S;Anderson GP;Holdsworth SR;Bardin PG
通讯作者：
Bardin PG
影响因子：
5.1
作者：
Giordano, Luca;Aneja, Manish K.;Sommer, Natascha;Alebrahimdehkordi, Nasim;Seraji, Alireza;Weissmann, Norbert;Rudolph, Carsten;Plank, Christian;Jacobs, Howard T.;Szibor, Marten
通讯作者：
Szibor, Marten