Published in:
Open Access 01-12-2017 | Short Communication
Role of second-hand smoke (SHS)-induced proteostasis/autophagy impairment in pediatric lung diseases
Published in: Molecular and Cellular Pediatrics | Issue 1/2017
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Background
Exposure to second-hand tobacco smoke (SHS) is one of the prime risk factors for chronic lung disease development. Smoking during pregnancy may lead to birth defects in the newborn that include pulmonary dysfunction, increased susceptibility to opportunistic pathogens, or initiation of childhood respiratory manifestations such as bronchopulmonary dysplasia (BPD). Moreover, exposure to SHS in early childhood can have negative impact on lung health, although the exact mechanisms are unclear. Autophagy is a crucial proteostatic mechanism modulated by cigarette smoke (CS) in adult lungs. Here, we sought to investigate whether SHS exposure impairs autophagy in pediatric lungs.
Methods
Pregnant C57BL/6 mice were exposed to room air or SHS for 14 days. The newborn pups were subsequently exposed to room air or SHS (5 h/day) for 1 or 14 days, and lungs were harvested. Soluble and insoluble protein fractions isolated from pediatric mice lungs were subjected to immunoblotting for ubiquitin (Ub), p62, VCP, HIF-1α, and β-actin.
Results
Our data shows that short-term exposure to SHS (1 or 14 days) leads to proteostasis and autophagy-impairment as evident by significant increase in accumulation of ubiquitinated proteins (Ub), p62 (impaired-autophagy marker) and valosin-containing protein (VCP) in the insoluble protein fractions of pediatric mice lungs. Moreover, increased HIF-1α levels in SHS-exposed mice lungs points towards a novel mechanism for SHS-induced lung disease initiation in the pediatric population. Validating the in vivo studies, we demonstrate that treatment of human bronchial epithelial cells (Beas2b cells) with the proteasome inhibitor (MG-132) induces HIF-1α expression that is controlled by co-treatment with autophagy-inducing drug, cysteamine.
Conclusions
SHS-exposure induced proteostasis/autophagy impairment can mediate the initiation of chronic lung disease in pediatric subjects. Hence, our data warrants the evaluation of proteostasis/autophagy-inducing drugs, such as cysteamine, as a potential therapeutic intervention strategy for SHS-induced pediatric lung diseases.
