New advances on structural and biological functions of ceramide in apoptotic/necrotic cell death and cancer

[摘要]

Recent data on the cellular ceramide functions and its involvement in the apoptotic/necrotic cell death as well as its anticarcinogenic properties are presented. The emphasis is on the connections between the ceramide and caspase signaling pathways during the apoptotic cell death process. Notably, the experimental strategies and pharmacological tools used for establishment of the role of ceramide in triggering cell death are described. Moreover, the importance of a compartmentation of endogenous ceramide within the plasma membrane microdomains, lysosomes and mitochondria is discussed. Information on the deregulated functions of ceramide and caspase signaling pathways in several metastatic cancer types is also presented.

[学科分类] 生物化学/生物物理

[关键词] Ceramide;Caveolae/raft structure;Mitochondrial apoptotic signal;Caspase;Apoptotic/necrotic cell death;Anticarcinogenic therapy;AIF;apoptosis-initiating factor;aSMase;acidic sphingomyelinase;CER;ceramide;Cyt c;cytochrome c;EGF;epidermal growth factor;eNOS;endothelial nitric oxide synthase;IL-1β;interleukin-1β;iNOS;inducible nitric oxide synthase;INF-γ;interferon-γ;nNOS;neuronal nitric oxide synthase;NOS;nitric oxide synthase;nSMase;neutral sphingomyelinase;OE;N-oleoylethanolamide;oxLDL;oxidized low density lipoprotein;PDGF;platelet-derived growth factor;PKC;protein kinase C;PI3K;phosphoinositide 3-kinase;ROS;reactive oxygen species;SM;sphingomyelin;TNF-α;tumor necrosis factor-α;TPA;12-O-tetradecanoylphorbol-13-acetate