Apoptosis induced by Trimethyltin chloride in human neuroblastoma cells SY5Y is regulated by a balance and cross-talk between NF-kappa B and MAPKs signaling pathways

作者：Qing Yan; Liang Yanfang; Du Qingqing; Fan Pan; Xu Hangong; Xu Yiping; Shi Nian^*

来源：Archives of Toxicology, 2013, 87(7): 1273-1285.

DOI：10.1007/s00204-013-1021-9

• Trimethyltin chloride (TMT)
• Nuclear factor kappa B (NF-kappa B)
• Mitogen-activated protein kinases (MAPKs)
• Apoptosis
• Human neuroblastoma cells SY5Y (SH-SY5Y)
• Cross-talk

Trimethyltin chloride (TMT) has been known as a classic neurotoxicant which can cause serious neuronal degeneration diseases. Nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinases (MAPKs) signaling pathways play pivotal role in the central nerves system. In the present study, the intracellular pathways involved in TMT-induced apoptosis on human neuroblastoma cells SY5Y (SH-SY5Y) were investigated. We observed high level of nuclear NF-kappa B p65 submit, activated JNK, ERK, and p38 by TMT exposure. In contrast, low level of Bcl-2 and XIAP (two known NF-kappa B-regulated endogenous anti-apoptotic molecules) was present. To further investigate the role of these pathways and the relationship between them, specific inhibitors were used and the alteration of each pathway was evaluated. Pretreatment with MG132, an inhibitor of proteasome activity, and BAY11-7082, an inhibitor of I kappa B alpha phosphorylation, both inhibited NF-kappa B p65 translocation and significantly promoted apoptosis. NF-kappa B inhibition also induced down-expression of Bcl-2 and XIAP, exaggerated JNK phosphorylation, and ERK inhibition. SP600125 and U0126, by blocking the phosphorylation of c-Jun and MEK1/2, inhibited JNK and ERK phosphorylation, respectively, and attenuated apoptosis significantly. JNK and ERK inhibition also induced I kappa B alpha degradation and NF-kappa B p65 translocation, leading to expression of Bcl-2 and XIAP. The detrimental role of MG132 and BAY11-7082 appears related to the exaggerated JNK phosphorylation. The SP600125 and U0126 neuroprotection appears related to NF-kappa B-regulated transcriptional control of Bcl-2 and XIAP. These results suggest that the cross-talk and a balance between NF-kappa B and MAPKs may be involved in TMT-induced apoptosis on SH-SY5Y cells.

• 出版日期2013-7
• 单位华中科技大学