Tags

Type your tag names separated by a space and hit enter

NF-kappaB mediates MPP+-induced apoptotic cell death in neuroblastoma cells SH-EP1 through JNK and c-Jun/AP-1.
Neurochem Int. 2010 Jan; 56(1):128-34.NI

Abstract

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in substantia nigra with unknown etiology. Neuropathology seen in the brains of PD patients can be closely mimicked by MPP(+)-induced neurotoxicity in vitro. In this study, we used an S-type human neuroblastoma cell line (SH-EP1) as a model to investigate the involvement of NF-kappaB and JNK pathways in MPP(+)-induced neurotoxicity. We show that NF-kappaB was activated by MPP(+) as evidenced by NF-kappaB p65 nuclear translocation, the increased DNA binding activity and a rapid phosphorylation of NF-kappaB inhibitor (IkappaBalpha). NF-kappaB partially mediated the neurotoxicity of MPP(+), as suggested by the reduction of MPP(+)-induced cell death by both a specific IkappaB kinase (IKK) inhibitor and a dominant negative form of IkappaBalpha (IkappaBalpha-M). Besides NF-kappaB, JNK and c-Jun/AP-1 were also activated upon MPP(+) stimulation. Inhibition of JNK activation with a specific JNK inhibitor partially reduced the MPP(+)-mediated cell death. Similarly, inhibition of c-Jun/AP-1 activation, either by a dominant negative c-Jun or c-Jun/AP-1 inhibitor, significantly attenuated MPP(+)-mediated cell death. These results suggest that both JNK and c-Jun/AP-1 activation are pro-apoptotic. Furthermore, we provide clear evidence for the existence of a crosstalk between the NF-kappaB and JNK signaling as MPP(+)-induced activation of JNK and c-Jun/AP-1 was strongly down-regulated in IkappaBalpha-M cells. In conclusion, we demonstrate that in SH-EP1 cells MPP(+)-induced neurotoxicity is partially mediated by NF-kappaB which in turn acts on the activation of JNK and c-Jun/AP-1. These results may point to a combined inhibition of NF-kappaB and JNK as a new approach to PD therapy.

Authors+Show Affiliations

Genomics & Genetics Division, School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19778565

Citation

Yang, Hai-Jie, et al. "NF-kappaB Mediates MPP+-induced Apoptotic Cell Death in Neuroblastoma Cells SH-EP1 Through JNK and C-Jun/AP-1." Neurochemistry International, vol. 56, no. 1, 2010, pp. 128-34.
Yang HJ, Wang L, Xia YY, et al. NF-kappaB mediates MPP+-induced apoptotic cell death in neuroblastoma cells SH-EP1 through JNK and c-Jun/AP-1. Neurochem Int. 2010;56(1):128-34.
Yang, H. J., Wang, L., Xia, Y. Y., Chang, P. N., & Feng, Z. W. (2010). NF-kappaB mediates MPP+-induced apoptotic cell death in neuroblastoma cells SH-EP1 through JNK and c-Jun/AP-1. Neurochemistry International, 56(1), 128-34. https://doi.org/10.1016/j.neuint.2009.09.010
Yang HJ, et al. NF-kappaB Mediates MPP+-induced Apoptotic Cell Death in Neuroblastoma Cells SH-EP1 Through JNK and C-Jun/AP-1. Neurochem Int. 2010;56(1):128-34. PubMed PMID: 19778565.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NF-kappaB mediates MPP+-induced apoptotic cell death in neuroblastoma cells SH-EP1 through JNK and c-Jun/AP-1. AU - Yang,Hai-Jie, AU - Wang,Lei, AU - Xia,Yin-Yan, AU - Chang,Piek-Ngoh, AU - Feng,Zhi-Wei, Y1 - 2009/09/22/ PY - 2009/09/14/received PY - 2009/09/15/accepted PY - 2009/9/26/entrez PY - 2009/9/26/pubmed PY - 2010/5/5/medline SP - 128 EP - 34 JF - Neurochemistry international JO - Neurochem Int VL - 56 IS - 1 N2 - Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in substantia nigra with unknown etiology. Neuropathology seen in the brains of PD patients can be closely mimicked by MPP(+)-induced neurotoxicity in vitro. In this study, we used an S-type human neuroblastoma cell line (SH-EP1) as a model to investigate the involvement of NF-kappaB and JNK pathways in MPP(+)-induced neurotoxicity. We show that NF-kappaB was activated by MPP(+) as evidenced by NF-kappaB p65 nuclear translocation, the increased DNA binding activity and a rapid phosphorylation of NF-kappaB inhibitor (IkappaBalpha). NF-kappaB partially mediated the neurotoxicity of MPP(+), as suggested by the reduction of MPP(+)-induced cell death by both a specific IkappaB kinase (IKK) inhibitor and a dominant negative form of IkappaBalpha (IkappaBalpha-M). Besides NF-kappaB, JNK and c-Jun/AP-1 were also activated upon MPP(+) stimulation. Inhibition of JNK activation with a specific JNK inhibitor partially reduced the MPP(+)-mediated cell death. Similarly, inhibition of c-Jun/AP-1 activation, either by a dominant negative c-Jun or c-Jun/AP-1 inhibitor, significantly attenuated MPP(+)-mediated cell death. These results suggest that both JNK and c-Jun/AP-1 activation are pro-apoptotic. Furthermore, we provide clear evidence for the existence of a crosstalk between the NF-kappaB and JNK signaling as MPP(+)-induced activation of JNK and c-Jun/AP-1 was strongly down-regulated in IkappaBalpha-M cells. In conclusion, we demonstrate that in SH-EP1 cells MPP(+)-induced neurotoxicity is partially mediated by NF-kappaB which in turn acts on the activation of JNK and c-Jun/AP-1. These results may point to a combined inhibition of NF-kappaB and JNK as a new approach to PD therapy. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/19778565/NF_kappaB_mediates_MPP+_induced_apoptotic_cell_death_in_neuroblastoma_cells_SH_EP1_through_JNK_and_c_Jun/AP_1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(09)00274-5 DB - PRIME DP - Unbound Medicine ER -