Deficiency Exacerbates Acrolein-Induced Lung Injury Through Mitochondrial Redox Environment Deterioration

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2018 Feb 20

PMID 29456784

Citations 11

Authors

Jung Hyun Park

Hyeong Jun Ku

Jin Hyup Lee

Jeen-Woo Park

Affiliations

Soon will be listed here.

Abstract

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP-dependent isocitrate dehydrogenase () regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of in acrolein-induced lung injury using short hairpin RNA- (shRNA-) transfected Lewis lung carcinoma (LLC) cells and -deficient ( ) mice. Downregulation of expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. deficiency also promoted acrolein-induced lung injury in knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in shRNA-transfected LLC cells and in knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from deficiency. In conclusion, deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in mice. The present study supports the central role of deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

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