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Ceramide Pathway

This image is a scaled-down version of the actual pathway image. It does not contain any links to the protein information pages.


The SM (Sphingomyelin) pathway is an evolutionarily conserved stress response system linking diverse environmental stresses (Ultraviolet, Heat Shock, Oxidative Stress, and Ionizing Radiation) to cellular effector pathways. Ceramide is the second messenger in this system and can be generated either by hydrolysis of SM through SM-specific PLC (Phospholipase-C) termed SMases (Sphingomyelinases) or by de novo synthesis through the enzyme Ceramide Synthase (Ref.1). There are two classes of SMase, acidic (A-Smase) and neutral (N-Smase). Stress stimuli such as, TNF-Alpha (Tumor Necrosis Factor-Alpha), lipopolysaccharide, and some chemotherapy drugs such as doxorubicin also mediate apoptosis by generation of the lipid second messenger, Ceramide. A specific interaction between the FAN (Factor Associated with N-Smase activation), protein and TNF-Alpha associated proteins (TRADD, TRAFs and RIP) regulates Ceramide production by N-Smase, a [...]


1.CD95 (Fas/APO-1) signals ceramide generation independent of the effector stage of apoptosis.
Grullich C, Sullards MC, Fuks Z, Merrill AH Jr, Kolesnick R.
J Biol Chem. 2000 Mar 24; 275(12): 8650-6.
2.Modulating sphingolipid biosynthetic pathway rescues photoreceptor degeneration.
Acharya U, Patel S, Koundakjian E, Nagashima K, Han X, Acharya JK.
Science. 2003 Mar 14; 299(5613): 1740-3.
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