Anti-aging Klotho Protects SH-SY5Y Cells Against Amyloid β1�42 Neurotoxicity: Involvement of Wnt1/pCREB/Nrf2/HO-1 Signaling

Sedighi, M. and Baluchnejadmojarad, T. and Afshin-Majd, S. and Amiri, M. and Aminzade, M. and Roghani, M. (2021) Anti-aging Klotho Protects SH-SY5Y Cells Against Amyloid β1�42 Neurotoxicity: Involvement of Wnt1/pCREB/Nrf2/HO-1 Signaling. Journal of Molecular Neuroscience, 71 (1). pp. 19-27.

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Alzheimer�s disease (AD) is considered a prevalent neurological disorder with a neurodegenerative nature in elderly people. Oxidative stress and neuroinflammation due to amyloid β (Aβ) peptides are strongly involved in AD pathogenesis. Klotho is an anti-aging protein with multiple protective effects that its deficiency is involved in development of age-related disorders. In this study, we investigated the beneficial effect of Klotho pretreatment at different concentrations of 0.5, 1, and 2 nM against Aβ1�42 toxicity at a concentration of 20 μM in human SH-SY5Y neuroblastoma cells. Our findings showed that Klotho could significantly and partially restore cell viability and decrease reactive oxygen species (known as ROS) and improve superoxide dismutase activity (SOD) in addition to reduction of caspase 3 activity and DNA fragmentation following Aβ1�42 challenge. In addition, exogenous Klotho also reduced inflammatory biomarkers consisting of nuclear factor-kB (NF-kB), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in Aβ-exposed cells. Besides, Klotho caused downregulation of Wnt1 level, upregulation of phosphorylated cyclic AMP response element binding (pCREB), and mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) with no significant alteration of epsilon isoform of protein kinase C (PKCε) after Aβ toxicity. In summary, Klotho could alleviate apoptosis, oxidative stress, and inflammation in human neuroblastoma cells after Aβ challenge and its beneficial effect is partially exerted through appropriate modulation of Wnt1/pCREB/Nrf2/HO-1 signaling. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: amyloid beta protein1-42; caspase 3; cyclic AMP responsive element binding protein; heme oxygenase 1; immunoglobulin enhancer binding protein; interleukin 1beta; Klotho protein; phosphoprotein; protein kinase C epsilon; reactive oxygen metabolite; recombinant protein; superoxide dismutase; transcription factor Nrf2; tumor necrosis factor; Wnt1 protein, Alzheimer disease; antiinflammatory activity; apoptosis; Article; cell viability; controlled study; DNA fragmentation; down regulation; enzyme activity; human; human cell; mRNA expression level; neuroprotection; neurotoxicity; oxidative stress; SH-SY5Y cell line; signal transduction; upregulation
Subjects: QZ Pathology
Depositing User: eprints admin
Date Deposited: 05 Apr 2021 07:53
Last Modified: 05 Apr 2021 07:53

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