Pulmonary fibrosis culprits

Isoketal-modified proteins as a potential therapeutic target of pulmonary fibrosis

08-Jun-2016 - USA

Isoketals (IsoKs) – highly reactive compounds formed when membrane lipids are attacked by free radicals – are emerging as a mechanistic link between pathogenic reactive oxygen species and disease progression. However, the identity of IsoK-modified proteins and whether isoketal generation is subject to genetic regulation remains unclear.

Stacey Mont, Michael L. Freeman , Ph.D., and colleagues found that the enzyme Nox2, which generates superoxide, and Nrf2-mediated antioxidant gene expression are key regulators of isoketals generated in pulmonary tissue.

Purification of IsoK-modified proteins followed by chromatography-mass spectrometry analysis revealed that proteins in numerous cellular pathways are susceptible to isoketal modification. Prominent modification occurred in a mouse model of radiation-induced pulmonary fibrosis and in human idiopathic pulmonary fibrosis. Modification inhibits protein degradation, which can induce programmed cell death (apoptosis).

These findings identify isoketal-modified proteins as a previously unrecognized feature of pulmonary fibrosis and as a potential therapeutic target for this currently untreatable disease.

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Topic World Mass Spectrometry

Mass spectrometry enables us to detect and identify molecules and reveal their structure. Whether in chemistry, biochemistry or forensics - mass spectrometry opens up unexpected insights into the composition of our world. Immerse yourself in the fascinating world of mass spectrometry!

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