Lipid Raft Redox Signaling Platforms in Endothelial Dysfunction

Abstract

In response to various stimuli, membrane lipid rafts (LRs) are clustered to aggregate or recruit NADPH oxidase subunits and related proteins in vascular endothelial cells (ECs), forming redox signaling platforms. These LR signaling platforms may play important roles in the normal regulation of endothelial function and in the development of endothelial dysfunction or injury under pathological conditions. This LR-mediated mechanism now takes center stage in cell signaling for the regulation of many cellular activities or cell function such as ECs redox signaling, phagosomal activity of phagocytes, and cell apopotosis of lymphocytes. This brief review summarizes current evidence that relates to the formation of LR redox signaling platforms and their features in ECs, the functional significance of these signaling platforms in mediating death receptor activation-induced endothelial dysfunction, and the mechanisms initiating or promoting the formation of these platforms. It is expected that information provided here will help readers to understand this new signaling mechanism and perhaps extend the LR signaling platform concept to other research areas related to death receptors, redox signaling, endothelial biology, and cell/molecular biology of the cardiovascular system.

Astrocytes, but Not Microglia, Rapidly Sense H2O2 via STAT6 Phosphorylation, Resulting in Cyclooxygenase-2 Expression and Prostaglandin Release

“…Lipid rafts are membrane microdomains enriched in cholesterol, sphingolipid, and phospholipids with long and saturated acyl chains that function as signaling platforms for the assembly of molecular-signaling modules during a number of cellular events (49). Several ROS-regulated cellular processes are also regulated through lipid rafts (50)(51)(52). Considering that phosphorylation status is the net result of the interactions of phosphatases and kinases, changes in the redox status and recruitment of these protein-modifying enzymes to lipid rafts by oxidative stimuli might underlie the differential sensitivity of the two cell types.…”

Anti–Dengue Virus Nonstructural Protein 1 Antibodies Cause NO-Mediated Endothelial Cell Apoptosis via Ceramide-Regulated Glycogen Synthase Kinase-3β and NF-κB Activation

“…In this study, we aimed to elucidate the relevant signaling pathway(s) in particular, the role of lipid rafts and ceramide. The formation of lipid rafts, the membrane microdomains that are enriched in cholesterol and glycosphingolipids, play an important role in cellular signaling in response to various stimuli (31)(32)(33)(34)(35). Ceramide, which is enriched in lipid rafts, acts as a second messenger of multiple extracellular stimuli in cell survival, inflammation, and apoptotic cell death (36)(37)(38)(39)(40)(41).…”

Lipid raft-dependent activation of dual oxidase 1/H2O2/NF-κB pathway in bronchial epithelial cells

“…In this regard, LRs are emerging as a critical mechanism to mediate the assembling of NOX subunits and consequent activation, leading to redox signaling (23,28,32,33,39). It is proposed that LRs consist of dynamic assembly lipids with saturated acyl chains such as sphingolipids or glycosphingolipids, in the exoplasmic leaflet of the membrane bilayer, and cholesterol in the inner leaflet (29,43).…”

“…It is proposed that LRs consist of dynamic assembly lipids with saturated acyl chains such as sphingolipids or glycosphingolipids, in the exoplasmic leaflet of the membrane bilayer, and cholesterol in the inner leaflet (29,43). Extraction of cholesterol by methyl-␤-cyclodextrin (MCD) is widely used to disrupt the integrity of the raft structure (28,29). Membrane LRs are able to form relatively larger macrodomains or platforms upon activation of individual receptors by ligand binding, where various signaling molecules can be recruited and aggregated to form signaling platforms or signalosomes (11,51), activating various signaling pathways (23,28,46).…”

“…Extraction of cholesterol by methyl-␤-cyclodextrin (MCD) is widely used to disrupt the integrity of the raft structure (28,29). Membrane LRs are able to form relatively larger macrodomains or platforms upon activation of individual receptors by ligand binding, where various signaling molecules can be recruited and aggregated to form signaling platforms or signalosomes (11,51), activating various signaling pathways (23,28,46). One of such signaling platforms was named as the LR redox signaling platform (22,50), which is recognized as a missing link between death receptors and NOX activation in endothelial cells (46).…”