Cigarette Smoke-Induced Proteostasis Imbalance in Obstructive Lung Diseases

Author(s): A. M. Cantin, M. V. Richter

Journal Name: Current Molecular Medicine

Volume 12 , Issue 7 , 2012

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The airway and alveolar surface is exposed daily to 8,000 L of air containing oxygen, particles, bacteria, allergens and pollutants, all of which have the potential to induce oxidative stress within cells. If one is also a cigarette smoker, then the exposure to reactive oxidants increases exponentially. More than any other tissue, the lung is at risk of undergoing oxidative changes in protein expression, structure and function. The oxidant burden of chronic cigarette smoke exposure can overwhelm the lung cells’ capacity to maintain proteostasis, a process of regulated protein synthesis, folding and turnover. Somewhat surprisingly, most chronic cigarette smokers do not develop chronic obstructive pulmonary disease (COPD), likely because cells initiate a highly effective unfolded protein response (UPR) in the presence of oxidant-derived endoplasmic reticulum (ER) stress that allows cells to survive. The UPR initiates several signaling pathways that decrease protein translation, limit cell cycle progression, increase protein degradation and chaperone-mediated protein folding, and activate the transcription factor Nrf2 that induces antioxidant gene expression. Each of these actions decreases ER stress in a process of “healthy proteostasis”. If these responses are insufficient, apoptosis ensues. In this article, we review the mechanisms of healthy and dysfunctional proteostasis related to cigarette smoke exposure and COPD.

Keywords: COPD, epithelium, ER stress, glutathione, Nrf2, oxidants, unfolded protein response, UPR, cigarette smoking, cancer , ischemic heart disease, chronic obstructive lung disease, chronic bronchitis, emphysema, tobacco pyrolysis

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Article Details

Year: 2012
Published on: 19 June, 2012
Page: [836 - 849]
Pages: 14
DOI: 10.2174/156652412801318746
Price: $65

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