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

ABSTRACT: Inflammation accompanied by severe oxidative stress plays a vital role in the orchestration and progression of neurodegeneration prevalent in chronic and acute central nervous system pathologies as well as in aging. The proinflammatory cytokine tumor necrosis factor-α (TNFα) elicits the formation of the bioactive ceramide by stimulating the hydrolysis of the membrane lipid sphingomyelin by sphingomyelinase activities. Ceramide stimulates the formation of reactive oxygen species (ROS) and apoptotic mechanisms in both neurons and nonneuronal cells, establishing a link between sphingolipid metabolism and oxidative stress. We demonstrated in SH-SY5Y human neuroblastoma cells and primary cortical neurons that TNFα is a potent stimulator of Mg(2+) -dependent neutral sphingomyelinase (Mg(2+) -nSM

SUBMITTER: Barth BM 

PROVIDER: S-EPMC3218197 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature