Figure 3.

Schematic model depicting apoptotic signaling pathways in HUVEC cells in response to combined USMB radiation treatments. Hydrolysis of sphingomyelin catalyzed by the enzyme sphingomyelinase (sphingomyelin phosphodiesterase 1 (SMPD1) and (sphingomyelin phosphodiesterase 2 (SMPD2)) results in ceramide production. The increased intracellular ceramide stimulates the release of mitochondrial cytochrome c promoting activation of procaspase 9 by inducing nucleotide binding to Apaf-1. Alternatively, De novo-synthesized ceramide is converted to galactosylceramide by UGT8 (UDP Glycosyltransferase 8). Galactosylceramide activates the iNKT cells which secrete perforin that assembles at the cell plasma membrane, allowing granzyme B to cause activation of the apoptotic cascade. From [25].