Astaxanthin inhibits apoptosis in a cell model of tauopathy by attenuating endoplasmic reticulum stress and unfolded protein response.

Autor: Shi H; School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China; Department of Bioengineering, Harbin Institute of Technology, Weihai, 264209, China., Zhao Y; School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China; Department of Bioengineering, Harbin Institute of Technology, Weihai, 264209, China. Electronic address: zhaoyan@hitwh.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Nov 15; Vol. 983, pp. 176962. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1016/j.ejphar.2024.176962
Abstrakt: The accumulation of misfolded proteins is a common pathological characteristic shared by many neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. The disruption of proteostasis triggers endoplasmic reticulum (ER) stress, during which the unfolded protein response (UPR) is initiated by the activation of protein kinase R-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6). These three branches of UPR signals act in concert to reduce the levels of abnormal proteins and restore ER homeostasis. However, the overactivation of UPR impairs cell function and induces apoptosis, which has been implicated in neurodegeneration. Astaxanthin is a xanthophyll carotenoid which has been shown to have neuroprotective effects in both cell and animal models; however, its effects on ER stress and UPR induced by disrupted proteostasis remain unclear. In this study, the effects of astaxanthin on ER stress and cytotoxicity were investigated in N2a cells stably expressing the pro-aggregant tau repeat domain carrying FTDP-17 mutation ΔK280 (Tau 4RD ΔK280). The results demonstrated that astaxanthin significantly inhibited Tau 4RD ΔK280-induced loss of cell viability and apoptosis, attenuating Tau 4RD ΔK280-induced caspase-3 activation and decrease of Bcl-2. Further studies revealed that astaxanthin treatment alleviated Tau 4RD ΔK280-induced ER stress and suppressed the activation of PERK, IRE1 and ATF6 signaling pathways. These findings suggested that astaxanthin might inhibit Tau 4RD ΔK280-induced cytotoxicity by attenuating UPR and ER stress. In addition, astaxanthin treatment resulted in a great reduction in the production of intracellular reactive oxygen species and a significant decrease in calcium influx induced by Tau 4RD ΔK280, which also contributed to the protective effects of astaxanthin against Tau 4RD ΔK280-induced cytotoxicity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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