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Salsolinol, an Endogenous Neurotoxin, Activates JNK and NF-κB Signaling Pathways in Human Neuroblastoma Cells

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Abstract

Salsolinol, an endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson’s disease (PD). In the present study, we have investigated the effects of salsolinol on the activation of two different signaling pathways that involve c-Jun N-terminal kinase (JNK), and nuclear factor-κB, (NF-κB) in human dopaminergic neuroblastoma SH-SY5Y cells. Salsolinol treatment caused upregulation in the levels of c-Jun and phosphorylated c-Jun. It also caused degradation of IκBα and translocated the active NF-κB into the nucleus. The binding activity of NF-κB to DNA was enhanced by salsolinol in a concentration dependent manner. Furthermore, salsolinol decreased the levels of the anti-apoptotic protein Bcl-2, and increased pro-apoptotic protein Bax, while enhancing the release of cytochrome-c from mitochondria. Mitochondrial complex-I activity was significantly decreased and reactive oxygen species (ROS) were increased in salsolinol treated cells. These results partly suggest that salsolinol-induced JNK and NF-κB signaling pathways may be involved in induction of apoptosis in human dopaminergic neurons, as seen in Parkinson’s disease.

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Acknowledgments

The authors acknowledge their appreciation of Dani Stramer for her excellent skills in typing this manuscript. S. Wanpen was supported by a doctoral scholarship program from the Ministry of University Affairs, Thailand. This study was supported by a grant, from NINDS #2R01 NS-34566-09 (M.E.).

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND, 58203, USA

    Sawitri Wanpen, Patcharee Kooncumchoo, Shaik Shavali, Piyarat Govitrapong & Manuchair Ebadi

  2. Department of Clinical Neuroscience, School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND, 58203, USA

    Manuchair Ebadi

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  1. Sawitri Wanpen
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Correspondence to Manuchair Ebadi.

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Wanpen, S., Kooncumchoo, P., Shavali, S. et al. Salsolinol, an Endogenous Neurotoxin, Activates JNK and NF-κB Signaling Pathways in Human Neuroblastoma Cells. Neurochem Res 32, 443–450 (2007). https://doi.org/10.1007/s11064-006-9246-0

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