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Apoptosis induced by trimethyltin chloride in human neuroblastoma cells SY5Y is regulated by a balance and cross-talk between NF-κB and MAPKs signaling pathways.
Arch Toxicol. 2013 Jul; 87(7):1273-85.AT

Abstract

Trimethyltin chloride (TMT) has been known as a classic neurotoxicant which can cause serious neuronal degeneration diseases. Nuclear factor κB (NF-κB) 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-κB p65 submit, activated JNK, ERK, and p38 by TMT exposure. In contrast, low level of Bcl-2 and XIAP (two known NF-κB-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 IκBα phosphorylation, both inhibited NF-κB p65 translocation and significantly promoted apoptosis. NF-κB 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 IκBα degradation and NF-κB 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-κB-regulated transcriptional control of Bcl-2 and XIAP. These results suggest that the cross-talk and a balance between NF-κB and MAPKs may be involved in TMT-induced apoptosis on SH-SY5Y cells.

Authors+Show Affiliations

Department of Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23423712

Citation

Qing, Yan, et al. "Apoptosis Induced By Trimethyltin Chloride in Human Neuroblastoma Cells SY5Y Is Regulated By a Balance and Cross-talk Between NF-κB and MAPKs Signaling Pathways." Archives of Toxicology, vol. 87, no. 7, 2013, pp. 1273-85.
Qing Y, Liang Y, Du Q, et al. Apoptosis induced by trimethyltin chloride in human neuroblastoma cells SY5Y is regulated by a balance and cross-talk between NF-κB and MAPKs signaling pathways. Arch Toxicol. 2013;87(7):1273-85.
Qing, Y., Liang, Y., Du, Q., Fan, P., Xu, H., Xu, Y., & Shi, N. (2013). Apoptosis induced by trimethyltin chloride in human neuroblastoma cells SY5Y is regulated by a balance and cross-talk between NF-κB and MAPKs signaling pathways. Archives of Toxicology, 87(7), 1273-85. https://doi.org/10.1007/s00204-013-1021-9
Qing Y, et al. Apoptosis Induced By Trimethyltin Chloride in Human Neuroblastoma Cells SY5Y Is Regulated By a Balance and Cross-talk Between NF-κB and MAPKs Signaling Pathways. Arch Toxicol. 2013;87(7):1273-85. PubMed PMID: 23423712.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apoptosis induced by trimethyltin chloride in human neuroblastoma cells SY5Y is regulated by a balance and cross-talk between NF-κB and MAPKs signaling pathways. AU - Qing,Yan, AU - Liang,Yanfang, AU - Du,Qingqing, AU - Fan,Pan, AU - Xu,Hangong, AU - Xu,Yiping, AU - Shi,Nian, Y1 - 2013/02/20/ PY - 2012/08/03/received PY - 2013/01/31/accepted PY - 2013/2/21/entrez PY - 2013/2/21/pubmed PY - 2013/10/18/medline SP - 1273 EP - 85 JF - Archives of toxicology JO - Arch Toxicol VL - 87 IS - 7 N2 - Trimethyltin chloride (TMT) has been known as a classic neurotoxicant which can cause serious neuronal degeneration diseases. Nuclear factor κB (NF-κB) 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-κB p65 submit, activated JNK, ERK, and p38 by TMT exposure. In contrast, low level of Bcl-2 and XIAP (two known NF-κB-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 IκBα phosphorylation, both inhibited NF-κB p65 translocation and significantly promoted apoptosis. NF-κB 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 IκBα degradation and NF-κB 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-κB-regulated transcriptional control of Bcl-2 and XIAP. These results suggest that the cross-talk and a balance between NF-κB and MAPKs may be involved in TMT-induced apoptosis on SH-SY5Y cells. SN - 1432-0738 UR - https://www.unboundmedicine.com/medline/citation/23423712/Apoptosis_induced_by_trimethyltin_chloride_in_human_neuroblastoma_cells_SY5Y_is_regulated_by_a_balance_and_cross_talk_between_NF_κB_and_MAPKs_signaling_pathways_ L2 - https://doi.org/10.1007/s00204-013-1021-9 DB - PRIME DP - Unbound Medicine ER -