Role of Nrf2 and Autophagy in Acute Lung Injury.

TitleRole of Nrf2 and Autophagy in Acute Lung Injury.
Publication TypeJournal Article
Year of Publication2016
Authorsde la Vega MRojo, Dodson M, Gross C, Manzour H, R Lantz C, Chapman E, Wang T, Black SM, Garcia JGN, Zhang DD
JournalCurr Pharmacol Rep
Volume2
Issue2
Pagination91-101
Date Published2016 Apr
ISSN Number2198-641X
Abstract

<p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. Characterized by severe inflammation and compromised lung function, ALI/ARDS result in very high mortality of affected individuals. Currently, there are no effective treatments for ALI/ARDS, and ironically, therapies intended to aid patients (specifically mechanical ventilation, MV) may aggravate the symptoms. Key events contributing to the development of ALI/ARDS are: increased oxidative and proteotoxic stresses, unresolved inflammation, and compromised alveolar-capillary barrier function. Since the airways and lung tissues are constantly exposed to gaseous oxygen and airborne toxicants, the bronchial and alveolar epithelial cells are under higher oxidative stress than other tissues. Cellular protection against oxidative stress and xenobiotics is mainly conferred by Nrf2, a transcription factor that promotes the expression of genes that regulate oxidative stress, xenobiotic metabolism and excretion, inflammation, apoptosis, autophagy, and cellular bioenergetics. Numerous studies have demonstrated the importance of Nrf2 activation in the protection against ALI/ARDS, as pharmacological activation of Nrf2 prevents the occurrence or mitigates the severity of ALI/ARDS. Another promising new therapeutic strategy in the prevention and treatment of ALI/ARDS is the activation of autophagy, a bulk protein and organelle degradation pathway. In this review, we will discuss the strategy of concerted activation of Nrf2 and autophagy as a preventive and therapeutic intervention to ameliorate ALI/ARDS.</p>

DOI10.1007/s40495-016-0053-2
Alternate JournalCurr Pharmacol Rep
PubMed ID27313980
PubMed Central IDPMC4905711
Grant ListR01 ES023758 / ES / NIEHS NIH HHS / United States
P30 ES006694 / ES / NIEHS NIH HHS / United States
P01 HL101902 / HL / NHLBI NIH HHS / United States
R01 HD039110 / HD / NICHD NIH HHS / United States
R01 HL067841 / HL / NHLBI NIH HHS / United States
R01 CA154377 / CA / NCI NIH HHS / United States
R01 HL060190 / HL / NHLBI NIH HHS / United States
P01 HL058064 / HL / NHLBI NIH HHS / United States
R01 ES015010 / ES / NIEHS NIH HHS / United States