Sustained Adenosine Caused Endothelial Mitochondrial Dysfunction: Implications for Cigarette Smoke‐Induced Increased Susceptibility to Acute Lung Injury

• DOI: 10.1096/fasebj.29.1_supplement.863.10
• Publication Date: 2021-06-21T19:30:23Z
• Authors: Eboni Chambers; Junsuk Ko; Diana Borgas; Julie Newton; Sharon Rounds; Qing Lu
• Keywords: Mitochondrial ROS; SOD2; Endothelial Dysfunction

Cigarette smoke (CS) has been independently associated with the development of acute lung injury (ALI). We have previously demonstrated that CS exposure increases adenosine levels in mice and sustained to causes endothelial by equilibrative nucleoside transporter (ENT) 1/2-dependent mechanism. In this study we hypothesize CS-induced increased injury, leading susceptibility ALI, via ENT1/2- mediated mitochondrial dysfunction. Using inhaled Pseudomonas aeruginosa, a clinically relevant model found pre-exposure exacerbated P. aeruginosa-induced injury. Pharmacological inhibition ENT1 attenuated edema inflammation. cultured cells, decreased basal respiration, reactive oxygen species (ROS), enhanced expression fission/fusion markers (Drp1 Mfn1) mitophagy marker (Parkin), promoted SOD2 expression. Inhibition ENT1/2 adenosine-induced ROS. Our data suggest elevated ENT1/2-dependent, oxidative stress-induced dysfunction, which may contribute ALI. PH-05-015 (Lu), P20GM103652 (Lu, Rounds), PULM-811-10S (Rounds), NIH NIEHS T32 ES007272 (supporting E. C.) Brown University Institutional UTRA J. K.)