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Icariin protects neurons from endoplasmic reticulum stress-induced apoptosis after OGD/R injury via suppressing IRE1α-XBP1 signaling pathway.
- Source :
-
Life sciences [Life Sci] 2020 Aug 15; Vol. 255, pp. 117847. Date of Electronic Publication: 2020 May 27. - Publication Year :
- 2020
-
Abstract
- Icariin (ICA), a flavonol glycoside isolated from Epimedium, has been considered as a potential alternative therapy for ischemic stroke. However, the protective mechanisms of ICA on cerebral ischemia-reperfusion (I/R) are not fully illuminated yet. The effects of ICA on ER stress and inflammatory response which were involved in the pathological process of cerebral I/R were investigated in vitro. Microglia and neurons were subjected to OGD/R. ICA was administrated to microglia 1 h before OGD and maintained 2 h throughout OGD. At 24 h after reoxygenation, the protein expression of IL-1 β, IL-6, TNF-α in the supernatant of microglia was measured using ELISA assay; neuronal apoptosis was assessed by TUNEL staining; and cell viability was detected using CKK-8 assay; the expression of IRE1α, XBP1u, XBP1s, and cleaved caspase-3 in neurons was examined by western blotting and qRT-PCR; the expression of p-IRE1α in neurons was detected by western blotting. We found that OGD/R induced the expression of IL-1 β, IL-6, TNF-α in the supernatant of microglia; OGD/R and these proinflammatory cytokines promoted the mRNA as well as protein expression of XBP1u, XBP1s and cleaved caspase-3, increased the ratio of p-IRE1α/IRE1α, as well as apoptosis, and decreased cell viability in primary cortical neurons, while ICA reversed the levels of the above factors. IRE1 overexpression enhanced ER stress as well as apoptosis, and impaired the protective effects of ICA. These results suggested that ICA can inhibit apoptosis in neurons after OGD/R through IRE1/XBP1 signaling pathway beside its anti-inflammatory effect.<br />Competing Interests: Declaration of competing interest The authors declared that they have no competing interests.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Anti-Inflammatory Agents pharmacology
Cell Survival drug effects
Cells, Cultured
Cytokines metabolism
Endoribonucleases metabolism
Glucose metabolism
Microglia drug effects
Microglia metabolism
Multienzyme Complexes metabolism
Neurons metabolism
Oxygen metabolism
Protein Serine-Threonine Kinases metabolism
Rats, Sprague-Dawley
Reperfusion Injury pathology
Signal Transduction drug effects
X-Box Binding Protein 1 metabolism
Apoptosis drug effects
Endoplasmic Reticulum Stress drug effects
Flavonoids pharmacology
Neurons drug effects
Reperfusion Injury drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 255
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32470450
- Full Text :
- https://doi.org/10.1016/j.lfs.2020.117847