Pulmonary fibrosis culprits
Isoketal-modified proteins as a potential therapeutic target of pulmonary fibrosis
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.
Original publication
Stacey Mont, Sean S. Davies, L. Jackson Roberts second, Raymond L. Mernaugh, W. Hayes McDonald, Brahm H. Segal, William Zackert, Jonathan A. Kropski, Timothy S. Blackwell, Konjeti R. Sekhar, James J. Galligan, Pierre P. Massion, Lawrence J. Marnett, Elizabeth L. Travis & Michael L. Freeman; "Accumulation of isolevuglandin-modified protein in normal and fibrotic lung"; Scientific Reports; 2016
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Original publication
Stacey Mont, Sean S. Davies, L. Jackson Roberts second, Raymond L. Mernaugh, W. Hayes McDonald, Brahm H. Segal, William Zackert, Jonathan A. Kropski, Timothy S. Blackwell, Konjeti R. Sekhar, James J. Galligan, Pierre P. Massion, Lawrence J. Marnett, Elizabeth L. Travis & Michael L. Freeman; "Accumulation of isolevuglandin-modified protein in normal and fibrotic lung"; Scientific Reports; 2016
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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!

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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