Title : Neutral sphingomyelinase activation precedes NADPH oxidase-dependent damage in neurons exposed to the proinflammatory cytokine tumor necrosis factor-α.

Pub. Date : 2012 Jan

PMID : 21932365






5 Functional Relationships(s)
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1 The proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) elicits the formation of the bioactive ceramide by stimulating the hydrolysis of the membrane lipid sphingomyelin by sphingomyelinase activities. Ceramides tumor necrosis factor Homo sapiens
2 The proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) elicits the formation of the bioactive ceramide by stimulating the hydrolysis of the membrane lipid sphingomyelin by sphingomyelinase activities. Ceramides tumor necrosis factor Homo sapiens
3 We demonstrated in SH-SY5Y human neuroblastoma cells and primary cortical neurons that TNFalpha is a potent stimulator of Mg(2+) -dependent neutral sphingomyelinase (Mg(2+) -nSMase) activity, and sphingomyelin hydrolysis, rather than de novo synthesis, was the predominant source of ceramide increases. Ceramides tumor necrosis factor Homo sapiens
4 Notably, TNFalpha provoked an NOX-dependent oxidative damage to sphingosine kinase-1, which generates sphingosine-1-phosphate, a ceramide metabolite associated with neurite outgrowth. Ceramides tumor necrosis factor Homo sapiens
5 Our studies suggest that TNFalpha-mediated activation of Mg(2+) -nSMase and NOX in neuronal cells not only produced the neurotoxic intermediates ceramide and ROS but also directly antagonized neuronal survival mechanisms, thus accelerating neurodegeneration. Ceramides tumor necrosis factor Homo sapiens