Cross Talk Between Ceramide and Redox Signaling: Implications for Endothelial Dysfunction and Renal Disease

Abstract

Recent studies have demonstrated that cross talk between ceramide and redox signaling modulates various cell activities and functions and contributes to the development of cardiovascular diseases and renal dysfunctions. Ceramide triggers the generation of reactive oxygen species (ROS) and increases oxidative stress in many mammalian cells and animal models. On the other hand, inhibition of ROS-generating enzymes or treatment of antioxidants impairs sphingomyelinase activation and ceramide production. As a mechanism, ceramide-enriched signaling platforms, special cell membrane rafts (MR) (formerly lipid rafts), provide an important microenvironment to mediate the cross talk of ceramide and redox signaling to exert a corresponding regulatory role on cell and organ functions. In this regard, activation of acid sphingomyelinase and generation of ceramide mediate the formation of ceramide-enriched membrane platforms, where trans-membrane signals are transmitted or amplified through recruitment, clustering, assembling, or integration of various signaling molecules. A typical such signaling platform is MR redox signaling platform that is centered on ceramide production and aggregation leading to recruitment and assembling of NADPH oxidase to form an active complex in the cell plasma membrane. This redox signaling platform not only conducts redox signaling or regulation but also facilitates a feedforward amplification of both ceramide and redox signaling. In addition to this membrane MR redox signaling platform, the cross talk between ceramide and redox signaling may occur in other cell compartments. This book chapter focuses on the molecular mechanisms, spatial–temporal regulations, and implications of this cross talk between ceramide and redox signaling, which may provide novel insights into the understanding of both ceramide and redox signaling pathways.

Acid sphingomyelinase mediates the noise‐induced liver disorder in mice

“…In the case of further downstream mechanisms, our work focused on ASM, one of the common responding molecules of various pathologic stimuli, which mediates hepatocytic damage by triggering endoplastic reticulum stress, autophagic disorder, lysosomal membrane permeabilization, oxidative stress and apoptosis. Acid sphingomyelinase is involved in liver disorders such as insulin resistance (I/R), lipogenesis, fibrosis and steatosis . We found that 5 days noise exposure raised ASM expression significantly which contributes to noticeable Cer accrual in hepatocytes.…”

Stimulation of Suicidal Erythrocyte Death by Naphthazarin

“…An oxidizing effect of naphthazarin has been shown previously [40,41]. In a wide variety of nucleated cells, ceramide triggers oxidative stress, which in turn favours sphingomyelinase activation and ceramide production [42]. Whether or not the interplay between oxidative stress and ceramide formation is similarly effective in erythrocytes remains to be shown.…”

K Ca 3.1 upregulation preserves endothelium‐dependent vasorelaxation during aging and oxidative stress

“…The presence of NADPH oxidase subunits or cofactors and antioxidant enzymes in lipid rafts (Li & Zhang, 2013) suggests that lipid rafts play an important role in the regulation of these enzymes. In addition, alteration of lipid rafts was suggested to occur in CerS2 null mice (Park et al ., 2013), and the function of lipid rafts is altered with aging (Fulop et al ., 2012).…”

“…Antioxidant enzymes are present in lipid rafts on cell membranes or have close relationships with lipid rafts (Li & Zhang, 2013). In addition, redox molecules, such as the NADPH oxidase subunits or cofactors, are present in lipid rafts (Li & Zhang, 2013). This evidence supports the view that lipid rafts are involved in initiating and transmitting redox signaling in cells.…”