Protective effect of saffron carotenoids against amyloid beta-induced neurotoxicity in differentiated PC12 cells via the unfolded protein response and autophagy.

Autor: Sanjari-Pour M; Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran., Faridi N; Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran., Wang P; College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, China., Bathaie SZ; Institute for Natural Products and Medicinal Plants, Tarbiat Modares University, Tehran, Iran.; UCLA-DOE Institute, University of California Los Angeles (UCLA), Los Angeles, California, USA.
Jazyk: angličtina
Zdroj: Phytotherapy research : PTR [Phytother Res] 2024 Oct; Vol. 38 (10), pp. 4923-4939. Date of Electronic Publication: 2023 Feb 15.
DOI: 10.1002/ptr.7773
Abstrakt: The preventive effect of saffron against Alzheimer's disease (AD) has been reported. Herein, we studied the effect of Cro and Crt, saffron carotenoids, on the cellular model of AD. The MTT assay, flow cytometry, and elevated p-JNK, p-Bcl-2, and c-PARP indicated the AβOs-induced apoptosis in differentiated PC12 cells. Then, the protective effects of Cro/Crt on dPC12 cells against AβOs were investigated in preventive and therapeutic modalities. Starvation was used as a positive control. RT-PCR and Western blot results revealed the reduced eIF2α phosphorylation and increased spliced-XBP1, Beclin1, LC3II, and p62, which indicate the AβOs-induced autophagic flux defect, autophagosome accumulation, and apoptosis. Cro and Crt inhibited the JNK-Bcl-2-Beclin1 pathway. They altered Beclin1 and LC3II and decreased p62 expressions, leading cells to survival. Cro and Crt altered the autophagic flux by different mechanisms. So, Cro increased the rate of autophagosome degradation more than Crt, while Crt increased the rate of autophagosome formation more than Cro. The application of 4μ8C and chloroquine as the inhibitors of XBP1 and autophagy, respectively, confirmed these results. So, augmentation of the survival branches of UPR and autophagy is involved and may serve as an effective strategy to prevent the progression of AβOs toxicity.
(© 2023 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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