Role of cigarette smoke-induced aggresome formation in chronic obstructive pulmonary disease-emphysema pathogenesis

Ian Tran, Changhoon Ji, Inzer Ni, Taehong Min, Danni Tang, Neeraj Vij

Research output: Contribution to journalArticlepeer-review

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 secondhand CS induces localization of ubiquitinated proteins in perinuclear spaces as aggresome bodies. Furthermore, we sought to determine the mechanism by which smoke-induced aggresome formation contributes to chronic obstructive pulmonary disease (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, whereas chronic CS-exposed murine model and human COPD-emphysema lung tissues were used for validation. In preliminary analysis, we observed a significant (P <0.01) increase in ubiquitinated protein aggregation in the insoluble protein fraction of CSE-treated Beas2b cells. We verified that CS-induced ubiquitin aggregrates are localized in the perinuclear spaces as aggresome bodies. These CS-induced aggresomes (P

Original languageEnglish (US)
Pages (from-to)159-173
Number of pages15
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume53
Issue number2
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

Keywords

  • Aggresomes
  • Autophagy
  • Chronic obstructive pulmonary disease
  • Cigarette smoke
  • Ubiquitin

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Medicine(all)

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