AJRCMB Articles in Press. Published on 09-December-2014 as 10.1165/rcmb.2014-0107OC

Page 1 of 58

Role of cigarette smoke-induced aggresome-formation in COPD-emphysema pathogenesis Ian Tran1,2, Changhoon Ji1,2, Inzer Ni1,2, Taehong Min1,2, Danni Tang1,2 and Neeraj Vij1,3,# 1

Department of Pediatric Respiratory Science, 2Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD and 3College of Medicine, Central Michigan University, Mt Pleasant, MI Running Title: Cigarette smoke induced aggresome-formation in COPD-emphysema

# Address of correspondence: Neeraj Vij Ph.D., Associate Professor of Molecular & Cell Biology College of Medicine | Central Michigan University 2630 Denison Drive, Room# 120 (Office) & 126-127 (Lab), College of Medicine Research Building | Mt. Pleasant MI 48859 Phone: 989-774-6453 | E-mail: [email protected]; [email protected]

Author contributions: IT, CJ, IN, TM and DT performed the experiments. IT, CJ, IN, TM, and NV analyzed the data. IT, CJ and NV wrote the manuscript. Support and declaration of interest: NV was supported by FAMRI-YCSA and NIH PS-OC (U54CA141868) grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 1

Copyright © 2014 by the American Thoracic Society

AJRCMB Articles in Press. Published on 09-December-2014 as 10.1165/rcmb.2014-0107OC

Page 2 of 58

Abstract Cigarette smoke (CS) exposure is known to induce proteostasis-imbalance that can initiate accumulation of ubiquitinated-proteins. Therefore, the primary goal of this study was to determine if first- and second- hand cigarette smoke (CS) induces localization of ubiquitinated-proteins in peri-nuclear spaces as aggresome bodies. Furthermore, we sought to determine the mechanism by which smoke induced aggresome-formation contributes to COPD-emphysema pathogenesis. Hence, Beas2b cells were treated with CS extract (CSE) for in vitro experimental analysis of CSinduced aggresome-formation by immunoblotting, microscopy, and reporter assays, while chronic-CS exposed murine model and human COPD-emphysema lung tissues were used for validation. In preliminary analysis, we observed a significant (p

Role of Cigarette Smoke-Induced Aggresome Formation in Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis.

Cigarette smoke (CS) exposure is known to induce proteostasis imbalance that can initiate accumulation of ubiquitinated proteins. Therefore, the prima...
2MB Sizes 0 Downloads 6 Views