Journal
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
Volume 77, Issue -, Pages 106-111Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2018.05.002
Keywords
Nitroalkene; Nitro-fatty acid; Nitric oxide; Nitrite; Peroxynitrite; Eicosanoid; Prostaglandin; Signaling; Proliferation; Fibrosis; Inflammation; Transcriptional regulation
Categories
Funding
- NIH [R37HL058115, P01-HL103455, R01-HL132550]
- Wellcome Trust [094143/Z/10/Z]
- British Heart Foundation [RG/12/ 11/29815]
- European Research Council
- Royal Society Wolfson Research Merit Award
- American Heart Association [17GRN33660955]
- [R01-GM125944]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL103455, R01HL132550, R01HL058115, R37HL058115] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM125944] Funding Source: NIH RePORTER
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Foundational advances in eicosanoid signaling, the free radical biology of oxygen and nitric oxide and mass spectrometry all converged to enable the discovery of nitrated unsaturated fatty acids. Due to the unique biochemical characteristics of fatty acid nitroalkenes, these species undergo rapid and reversible Michael addition of biological nucleophiles such as cysteine, leading to the post-translational modification of low molecular weight and protein thiols. This capability has led to the present understanding that nitro-fatty acid reaction with the alkylation-sensitive cysteine proteome leads to physiologically-beneficial alterations in transcriptional regulatory protein function, gene expression and in vivo rodent model responses to metabolic and inflammatory stress. These findings motivated the preclinical and clinical development of nitro-fatty acids as new drug candidates for treating acute and chronic metabolic and inflammatory disorders.
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