Cell signalling by oxidized lipids and the role of reactive oxygen species in the endothelium.
The controlled formation of ROS (reactive oxygen species) and RNS (reactive nitrogen species) is now known to be critical in cellular redox signalling. As with the more familiar phosphorylation-dependent signal transduction pathways, control of protein function is mediated by the post-translational modification at specific amino acid residues, notably thiols. Two important classes of oxidant-derived signalling molecules are the lipid oxidation products, including those with electrophilic reactive centres, and decomposition products such as lysoPC (lysophosphatidylcholine). The mechanisms can be direct in the case of electrophiles, as they can modify signalling proteins by post-translational modification of thiols. In the case of lysoPC, it appears that secondary generation of ROS/RNS, dependent on intracellular calcium fluxes, can cause the secondary induction of H2O2 in the cell. In either case, the intracellular source of ROS/RNS has not been defined. In this respect, the mitochondrion is particularly interesting since it is now becoming apparent that the formation of superoxide from the respiratory chain can play an important role in cell signalling, and oxidized lipids can stimulate ROS formation from an undefined source. In this short overview, we describe recent experiments that suggest that the cell signalling mediated by lipid oxidation products involves their interaction with mitochondria. The implications of these results for our understanding of adaptation and the response to stress in cardiovascular disease are discussed.
Zmijewski
J W
JW
Department of Pathology, University of Alabama at Birmingham, AL, USA.
Landar
A
A
Watanabe
N
N
Dickinson
D A
DA
Noguchi
N
N
Darley-Usmar
V M
VM
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D008077:Lipoproteins, LDL; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein