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Ceramide ratios are affected by cigarette smoke but not heat-not-burn or e-vapor aerosols across four independent mouse studies
Life Sciences ( IF 6.1 ) Pub Date : 2020-11-12 , DOI: 10.1016/j.lfs.2020.118753
Oksana Lavrynenko , Bjoern Titz , Sophie Dijon , Daniel Dos Santos , Catherine Nury , Thomas Schneider , Emmanuel Guedj , Justyna Szostak , Athanasios Kondylis , Blaine Phillips , Kim Ekroos , Florian Martin , Manuel C. Peitsch , Julia Hoeng , Nikolai V. Ivanov

Aims

Smoking is an important risk factor for the development of chronic obstructive pulmonary disease and cardiovascular diseases. This study aimed to further elucidate the role of ceramides, as a key lipid class dysregulated in disease states.

Main methods

In this article we developed and validated LC–MS/MS method for ceramides (Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1(15Z)) for the absolute quantification. We deployed it together with proteomics and transcriptomic analysis to assess the effects of cigarette smoke (CS) from the reference cigarette as well as aerosols from heat-not-burn (HnB) tobacco and e-vapor products in apolipoprotein E-deficient (ApoE−/−) mice over several time points.

Key findings

In the lungs, CS exposure substantially elevated the ratios of Cer(d18:1/24:0) and Cer(d18:1/24:1) to Cer(d18:1/18:0) in two independent ApoE−/− mouse inhalation studies. Data from previous studies, in both ApoE−/− and wild-type mice, further confirmed the reproducibility of this finding. Elevation of these ceramide ratios was also observed in plasma/serum, the liver, and—for the Cer(d18:1/24:1(15Z)) to Cer(d18:1/18:0) ratio—the abdominal aorta. Also, the levels of acid ceramidase (Asah1) and glucocerebrosidase (Gba)—lysosomal enzymes involved in the hydrolysis of glucosylceramides—were consistently elevated in the lungs after CS exposure. In contrast, exposure to HnB tobacco product and e-vapor aerosols did not induce significant changes in the ceramide profiles or associated enzymes.

Significance

Our work in mice contributes to the accumulating evidence on the importance of ceramide ratios as biologically relevant markers for respiratory disorders, adding to their already demonstrated role in cardiovascular disease risk assessment in humans.



中文翻译:

在四项独立的小鼠研究中,神经酰胺比率受香烟烟雾的影响,但不受热不燃烧或电子蒸发气溶胶的影响

目的

吸烟是导致慢性阻塞性肺疾病和心血管疾病的重要危险因素。这项研究旨在进一步阐明神经酰胺的作用,神经酰胺是在疾病状态下失调的关键脂质类。

主要方法

在本文中,我们开发并验证了用于神经酰胺(Cer(d18:1/16:0),Cer(d18:1/18:0),Cer(d18:1/24:0)和Cer的LC-MS / MS方法(d18:1/24:1(15Z))进行绝对定量,我们将其与蛋白质组学和转录组学分析一起部署,以评估参考香烟中的香烟烟雾(CS)以及非燃烧产生的气溶胶的影响载脂蛋白E缺乏症(ApoE -/-)小鼠在多个时间点的(HnB)烟草和电子蒸发产品。

主要发现

在肺中,CS暴露在两个独立的ApoE中显着提高了Cer(d18:1/24:0)和Cer(d18:1/24:1)与Cer(d18:1/18:0)的比率-/-小鼠吸入研究。来自先前研究的数据,均在ApoE中-/-和野生型小鼠,进一步证实了这一发现的可重复性。在血浆/血清,肝脏和Cer(d18:1/24:1(15Z))与Cer(d18:1/18:0)之比的腹主动脉中,这些神经酰胺比率也升高。同样,暴露于CS后,肺中酸性神经酰胺酶(Asah1)和葡萄糖脑苷脂酶(Gba)的水平(参与糖基神经酰胺水解的溶酶体酶)持续升高。相反,暴露于HnB烟草产品和e-蒸气气雾剂不会引起神经酰胺谱或相关酶的显着变化。

意义

我们在小鼠中的工作为神经酰胺比率作为呼吸系统疾病的生物学相关标志物的重要性提供了越来越多的证据,并进一步证明了它们在人类心血管疾病风险评估中的作用。

更新日期:2020-11-13
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