The essential role of ERK in 4-oxo-2-nonenal-mediated cytotoxicity in SH-SY5Y human neuroblastoma cells.

摘要: Lipid peroxidation byproducts, such as 4-hydroxynonenal (HNE) and 4-oxo-2-nonenal (ONE), induce cell death in a wide variety of types, partly by modulating intracellular signaling pathways. However, the specific mechanisms involved, particularly for ONE, are unclear while c-Jun N-terminal kinase (JNK) has been shown to be essential HNE-mediated cytotoxicity. In this study, we examined role mitogen-activated protein kinases pathways ONE-induced cytotoxicity SH-SY5Y human neuroblastoma cells found that ONE strongly induces phosphorylation extracellular signal-regulated (ERK) JNK, but not p38 MAPK. Interestingly, transient exposure resulted death, which contrasts with toxicity. Importantly, blocking ERK pathway, JNK protected against indicating striking difference between ONE- mechanisms. Furthermore, inhibition reduced p53, key modulator cellular stress response, proteolytic cleavage poly (ADP-ribose) polymerase (PARP), hallmark apoptosis. Overall, these data suggest plays an ONE-mediated is upstream component p53-mediated