Ladostigil Attenuates Induced Oxidative Stress in Human Neuroblast-like SH-SY5Y Cells
1
Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
2
Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
*
Author to whom correspondence should be addressed.
Academic Editors: Wen-Chi Hou, Wei-Jan Huang and Rita P.-Y. Chen
Biomedicines 2021, 9(9), 1251; https://doi.org/10.3390/biomedicines9091251
Received: 13 August 2021
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Revised: 14 September 2021
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Accepted: 16 September 2021
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Published: 17 September 2021
(This article belongs to the Topic Bioactive Natural Products and Synthetic Small Molecules as Potential Investigational Treatments for Neurodegenerative Diseases)
A hallmark of the aging brain is the robust inflammation mediated by microglial activation. Pathophysiology of common neurodegenerative diseases involves oxidative stress and neuroinflammation. Chronic treatment of aging rats by ladostigil, a compound with antioxidant and anti-inflammatory function, prevented microglial activation and learning deficits. In this study, we further investigate the effect of ladostigil on undifferentiated SH-SY5Y cells. We show that SH-SY5Y cells exposed to acute (by H2O2) or chronic oxidative stress (by Sin1, 3-morpholinosydnonimine) induced apoptotic cell death. However, in the presence of ladostigil, the decline in cell viability and the increase of oxidative levels were partially reversed. RNA-seq analysis showed that prolonged oxidation by Sin1 resulted in a simultaneous reduction of the expression level of endoplasmic reticulum (ER) genes that participate in proteostasis. By comparing the differential gene expression profile of Sin1 treated cells to cells incubated with ladostigil before being exposed to Sin1, we observed an over-expression of Clk1 (Cdc2-like kinase 1) which was implicated in psychophysiological stress in mice and Alzheimer’s disease. Ladostigil also suppressed the expression of Ccpg1 (Cell cycle progression 1) and Synj1 (Synaptojanin 1) that are involved in ER-autophagy and endocytic pathways. We postulate that ladostigil alleviated cell damage induced by oxidation. Therefore, under conditions of chronic stress that are observed in the aging brain, ladostigil may block oxidative stress processes and consequently reduce neurotoxicity.
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Keywords:
Alzheimer’s disease; neurodegenerative disease; mitophagy; microglial activation; RNA-seq; UPR; ER stress
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MDPI and ACS Style
Zohar, K.; Lezmi, E.; Eliyahu, T.; Linial, M. Ladostigil Attenuates Induced Oxidative Stress in Human Neuroblast-like SH-SY5Y Cells. Biomedicines 2021, 9, 1251. https://doi.org/10.3390/biomedicines9091251
AMA Style
Zohar K, Lezmi E, Eliyahu T, Linial M. Ladostigil Attenuates Induced Oxidative Stress in Human Neuroblast-like SH-SY5Y Cells. Biomedicines. 2021; 9(9):1251. https://doi.org/10.3390/biomedicines9091251
Chicago/Turabian StyleZohar, Keren, Elyad Lezmi, Tsiona Eliyahu, and Michal Linial. 2021. "Ladostigil Attenuates Induced Oxidative Stress in Human Neuroblast-like SH-SY5Y Cells" Biomedicines 9, no. 9: 1251. https://doi.org/10.3390/biomedicines9091251
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