Mol. Cells 2017; 40(4): 280~290
Neuroprotective Effects of Protein Tyrosine Phosphatase 1B Inhibition against ER Stress-Induced Toxicity
Yu-Mi Jeon1, Shinrye Lee1, Seyeon Kim1, Younghwi Kwon1, Kiyoung Kim2, Chang Geon Chung3,
Seongsoo Lee4, Sung Bae Lee3, and Hyung-Jun Kim1,*
1Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Daegu 41068, Korea, 2Department of
Medical Biotechnology, Soonchunhyang University, Asan 31538, Korea, 3Department of Brain & Cognitive Sciences, Daegu
Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea, 4Gwangju Center, Korea Basic Science Institute
(KBSI), Gwangju 61186, Korea
Received December 30, 2016; Revised March 21, 2017; Accepted March 22, 2017.; Published online March 28, 2017.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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Several lines of evidence suggest that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Protein tyrosine phosphatase 1B (PTP1B) is known to regulate the ER stress signaling pathway, but its role in neuronal systems in terms of ER stress remains largely unknown. Here, we showed that rotenone-induced toxicity in human neuroblastoma cell lines and mouse primary cortical neurons was ameliorated by PTP1B inhibition. Moreover, the increase in the level of ER stress markers (eIF2alpha phosphorylation and PERK phosphorylation) induced by rotenone treatment was obviously suppressed by concomitant PTP1B inhibition. However, the rotenone-induced production of reactive oxygen species (ROS) was not affected by PTP1B inhibition, suggesting that the neuroprotective effect of the PTP1B inhibitor is not associated with ROS production. Moreover, we found that MG132-induced toxicity involving proteasome inhibition was also ameliorated by PTP1B inhibition in a human neuroblastoma cell line and mouse primary cortical neurons. Consistently, downregulation of the PTP1B homologue gene in Drosophila mitigated rotenone- and MG132-induced toxicity. Taken together, these findings indicate that PTP1B inhibition may represent a novel therapeutic approach for ER stress-mediated neurodegenerative diseases.
Keywords: endoplasmic reticulum stress (ER Stress), MG132, reactive oxygen species (ROS), rotenone, ubiquitin proteasome system

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