Cigarette smoke increases cardiomyocyte ceramide accumulation and inhibits mitochondrial respiration

BMC Cardiovascular Disorders

Research Article

Adam C Swensen¹  Trevor S Tippetts²  Kurtis J Simmons²  Duane R Winden²  Mikayla O Thatcher²  Rex R Saito²  Michael B Nelson²  Paul R Reynolds²  Benjamin T Bikman²  Tyler B Condie²  Allan M Judd² 

[1] Department of Chemistry and Biochemistry, Brigham Young University, 84602, Provo, UT, USA;Department of Physiology and Developmental Biology and Chemistry, Brigham Young University, 84602, Provo, UT, USA;

关键词: Ceramide;    Mitochondrial Respiration;    Smoke Exposure;    Cigarette Smoke Extract;    Cigarette Smoke Exposure;   

DOI  :  10.1186/1471-2261-14-165

 received in 2014-10-06, accepted in 2014-11-17,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundCigarette smoking is a common and lethal worldwide habit, with considerable mortality stemming from its deleterious effects on heart function. While current theories posit altered blood lipids and fibrinogen metabolism as likely mediators, none have explored the role of the sphingolipid ceramide in exacerbating heart function with smoke exposure. Ceramide production is a consequence of cigarette smoke in the lung, and considering ceramide’s harmful effects on mitochondrial function, we sought to elucidate the role of ceramide in mediating smoke-induced altered heart mitochondrial respiration.MethodsLung cells (A549) were exposed to cigarette smoke extract (CSE) and heart cells (H9C2) were exposed to the lung-cell conditioned medium. Adult male mice were exposed sidestream cigarette smoke for 8 wk with dietary intervention and ceramide inhibition. Ceramides and heart cell or myocardial mitochondrial respiration were determined.ResultsLung cell cultures revealed a robust response to cigarette smoke extract in both production and secretion of ceramides. Heart cells incubated with lung-cell conditioned medium revealed a pronounced inhibition of myocardial mitochondrial respiration, though this effect was mitigated with ceramide inhibition via myriocin. In vivo, heart ceramides increased roughly 600% in adult mice with long-term sidestream cigarette smoke exposure. This resulted in a significant ceramide-dependent reduction in left myocardial mitochondrial respiration, as heart mitochondria from the mice exposed to both smoke and myriocin injections respired normally.ConclusionsThese results suggest ceramide to be an important mediator of altered myocardial mitochondrial function with cigarette smoke exposure. Thus, anti-ceramide therapies might be considered in the future to protect heart mitochondrial function with smoke exposure.

【 授权许可】

Unknown   
© Tippetts et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.