Fig. 8: Schematic overview of CAV1-dependent ASMase/ceramide signaling in EC. | Cell Death & Disease

Fig. 8: Schematic overview of CAV1-dependent ASMase/ceramide signaling in EC.

From: Caveolin-1 regulates the ASMase/ceramide-mediated radiation response of endothelial cells in the context of tumor–stroma interactions

Fig. 8: Schematic overview of CAV1-dependent ASMase/ceramide signaling in EC.The alternative text for this image may have been generated using AI.

Under normal (steady-state) conditions, ASMase is located in lysosomes (CAV1-proficient EC, upper panel, left). Upon stress induction by ionizing radiation (IR), ASMase is translocated to the plasma membrane, presumably facilitated by CAV1-abundant regions (lower panel, left). Thereby, IR leads to a rapidly increased ASMase activity, followed by ceramide generation (specifically of C16 and C24), which goes along with formation of large lipid platforms, and altered signal transduction directly affecting the p38/HSP27/MK2/AKT axis. The IR-induced remodeling of plasma membrane prior signaling implicates that CAV1 and ASMase-dependent ceramide generation are essential for stress-responsive cell-fate decisions like survival and/or cell death. CAV1 downregulation or absence in EC caused a constitutively upregulated ASMase activity that facilitates the increased generation of ceramide and specifically of the ceramide species C16 and C24 (upper panel, right). The resulting increase in (stable) large lipid platform formation permanently alters then the ceramide-dependent signaling of the p38/HSP27/MK2/AKT axis pathway finally priming EC apoptosis. Upon IR-induced stress, increased ceramide levels further increased membrane remodeling resulting in an amplified LLP/signalosome signaling finally leading to increased HSP27 activation, AKT deactivation, and then EC apoptosis (lower panel, right). Elevated ASMase/ceramide signaling in CAV1(−) EC might impact on adjacent tumor cell’s survival and growth in a negative manner.

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