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[Kalliste]

 

Nature Medicine | Article

Mitochondrial iron chelation ameliorates cigarette smoke–induced bronchitis and emphysema in mice

• Published online
• 11 January 2016

 

Abstract  

Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element–binding protein 2 (IRP2) as an important COPD susceptibility gene and have shown that IRP2 protein is increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RNA immunoprecipitation followed by sequencing (RIP-seq), RNA sequencing (RNA-seq), and gene expression and functional enrichment clustering analysis, we identified Irp2 as a regulator of mitochondrial function in the lungs of mice. Irp2 increased mitochondrial iron loading and levels of cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice, which had higher mitochondrial iron loading, showed impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas mice deficient in the synthesis of cytochrome c oxidase, which have reduced COX, were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-induced impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.

Subject terms:

• Experimental models of disease
• Iron
• Mechanisms of disease
• Respiratory tract diseases
• Translational research

At a glance Figures

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[Ark]

mitochondrial iron chelator?

[Kalliste]

Could not get the whole article. Might have been Tiron.

 

Edit:

 

 

Normal mice that were given deferiprone, an FDA-approved iron-chelating drug, and then exposed to cigarette smoke didn’t develop the COPD-like disease. In animals that had already developed the disease, the drug improved symptoms and lowered mitochondrial iron levels.

 

Edited by Cosmicalstorm, 17 January 2016 - 07:12 AM.