Nitrated lipids: A class of cell-signaling molecules
- Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226
It is becoming increasingly evident that the inflammatory oxidants reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive halogen species (RHS) mediate diverse pathologic processes in cardiovascular, pulmonary, and neurodegenerative diseases (1, 2). RNS (peroxynitrite, nitrogen-dioxide radical, or nitronium ion) are formed from the rapid reaction between ROS (superoxide) and nitric oxide (3), oxidation of nitrite anion by peroxidases and ROS (hydrogen peroxide) (4), or oxidation of nitrite anion by RHS (hypochlorous acid) (5). RNS react with carbohydrates, DNA bases, protein tyrosine/tryptophan, and unsaturated fatty acids to form relatively stable nitrated products (6). Investigators in this area are now focusing on the role of nitrated biomolecules on cell signaling and evaluating their cellular abundance, metabolism, and bioactivity (7). In this issue of PNAS, Baker et al. (8) report the identification and quantitation of allylic nitro derivatives of linoleic acid (termed LNO2 or nitrolinoleate) in healthy human blood samples. Data shown in this study indicate that the concentration of LNO2 found in red cells and plasma represents the single largest pool of bioactive oxides of nitrogen in the vasculature. This work also represents the convergence of antiinflammatory (•NO-dependent) and proinflammatory (oxidized lipid-dependent) cell-signaling pathways. Clearly, this is an exciting finding that will likely have profound implications in advancing our understanding of inflammatory processes.
The “Molecular Lens” Effect Induced by the Hydrophobicity of Membranes
The first obvious question is: Why should we be concerned about lipid nitration? The hydrophobic environment of biological membranes acts as a “molecular lens” and significantly enhances nitration, oxidation, and nitrosation reactions (9). Nitrogen oxides (•NO, NO2, and N2O3) will freely diffuse and concentrate into the hydrophobic membrane (9–11). Both the unprotonated and protonated forms of peroxynitrite (ONOO– and ONOOH) have been reported to cross the lipid membrane through an ion channel or by passive …
