Lipid Raft Redox Signaling: Molecular Mechanisms in Health and Disease

Abstract

Lipid rafts, the sphingolipid and cholesterol-enriched membrane microdomains, are able to form different membrane macrodomains or platforms upon stimulations, including redox signaling platforms, which serve as a critical signaling mechanism to mediate or regulate cellular activities or functions. In particular, this raft platform formation provides an important driving force for the assembling of NADPH oxidase subunits and the recruitment of other related receptors, effectors, and regulatory components, resulting, in turn, in the activation of NADPH oxidase and downstream redox regulation of cell functions. This comprehensive review attempts to summarize all basic and advanced information about the formation, regulation, and functions of lipid raft redox signaling platforms as well as their physiological and pathophysiological relevance. Several molecular mechanisms involving the formation of lipid raft redox signaling platforms and the related therapeutic strategies targeting them are discussed. It is hoped that all information and thoughts included in this review could provide more comprehensive insights into the understanding of lipid raft redox signaling, in particular, of their molecular mechanisms, spatial-temporal regulations, and physiological, pathophysiological relevances to human health and diseases. Antioxid. Redox Signal. 15, 1043-1083.

Antidepressant Drug, Desipramine, Alleviates Allergic Rhinitis by Regulating Treg and Th 17 Cells

“…The macromolecular proteins and molecules being recruited to the platform are intended to implement and amplify the signals (29). Desipramine could suppress the small lipid rafts to fuse into large platforms by decreasing the production of ceramide as a result of inhibiting the activity of acidic sphingomyelinase, thus leading to some negative effects on the initiation of downstream signal transduction (30); Moreover, desipramine also inhibits the infiltration of various inflammatory cells and the production ofinflammatory mediators (26). It is possible that the combined effects of desipramine lead to the relief ofAR inflammation by this drug.…”

Trafficking of PrPcto mitochondrial raft-like microdomains during cell apoptosis

“…Finally, since PrP C raft-mediated and (4) the mitochondrial oxidative phosphorylation and ATP production. 31 Both mitochondria depolarization and cytochrome c release are dependent on raft-like microdomain integrity, since the disruption of raft-like microdomains by methyl-β-cyclodextrin prevented mitochondria depolarization or cytochrome c release.…”

The trail to deadly membrane rafts

“…Accordingly, TRAIL may stimulate or inhibit apoptosis. TRAIL-induced apoptosis involves activation of acid sphingomyelinase with subsequent generation of ceramide and formation of membrane signaling platforms via clustering of membrane rafts, outer cell membrane domains assembling cholesterol and lipids with saturated acyl chains, such as sphingolipids and glycosphingolipids [2]. Those platforms are particularly important for redox signaling, as they recruit several molecules decisive for O 2 − production, such as NADPH oxidase subunits, gp91 phox , p47 phox , and Rac GTPase [2].…”

“…TRAIL-induced apoptosis involves activation of acid sphingomyelinase with subsequent generation of ceramide and formation of membrane signaling platforms via clustering of membrane rafts, outer cell membrane domains assembling cholesterol and lipids with saturated acyl chains, such as sphingolipids and glycosphingolipids [2]. Those platforms are particularly important for redox signaling, as they recruit several molecules decisive for O 2 − production, such as NADPH oxidase subunits, gp91 phox , p47 phox , and Rac GTPase [2]. In this issue, Li et al [3] provide compelling evidence that in coronary arterial endothelial cells TRAIL leads to fusion of lysosomes with the cell membrane as well as formation of ceramide and ganglioside G M1 -rich membrane rafts, which in turn provide redox signaling platforms for the stimulation of O 2 − production.…”