Chrysin inhibits ferroptosis of cerebral ischemia/reperfusion injury via regulating HIF-1α/CP loop - 27/04/24
Abstract |
Chrysin is a natural flavonoid with powerful neuroprotective capacity. Cerebral ischemia/reperfusion injury (CIRI) is associated with oxidative stress and ferroptosis. Hypoxia-inducible factor 1α (HIF-1α) and ceruloplasmin (CP) are the critical targets for oxidation reactions and iron transport. But the regulatory mechanism between them is still unclear. Transient middle cerebral artery occlusion (tMCAO) model in rats and oxygen and glucose deprivation/re-oxygenation (OGD/R) model in PC12 cells were applied. Pathological tissue staining and biochemical kit were used to evaluate the effect of chrysin. The relationship between HIF-1α and CP was verified by transcriptomics, qRT-PCR and Western blot. In CIRI, HIF-1α/CP loop was discovered to be the regulatory pathway of ferroptosis. CIRI led to activation and nuclear translocation of HIF-1α, which promoted CP transcription and translation, and downstream ferroptosis. Inhibition of HIF-1α had opposite effect on CP and ferroptosis regulation. Overexpression of CP increased the expression of HIF-1α, nevertheless, inhibited the nuclear translocation of HIF-1α and alleviated CIRI. Silencing CP promoted HIF-1α elevation in nucleus and aggravated CIRI. Mechanistically, chrysin restrained HIF-1α nuclear translocation, thereby inhibiting CP transcription and translation, which in turn reduced downstream HIF-1α expression and mitigated ferroptosis in CIRI. Our results highlight chrysin restrains ferroptosis in CIRI through HIF-1α/CP loop.
El texto completo de este artículo está disponible en PDF.Highlights |
• | CIRI causes lipid peroxidation and ferroptosis of neurons. |
• | Chrysin has anti-CIRI, antioxidant and anti-ferroptosis pharmacological effects. |
• | Chrysin inhibits ferroptosis in CIRI via HIF-1α/CP loop. |
Abbreviations : AAV, ACSL4, CBF, CIRI, CP, DMOG, Fe, GPX4, HE, HIF-1α, IF, IHC, LD50, LI, LPO, MDA, OGD/R, QRT-PCR, ROS, SLC7A11, SOD, TEM, TF, TFR1, TMCAO, TTC, WB, YC-1
Keywords : Chrysin, Cerebral ischemia/reperfusion injury (CIRI), Ferroptosis, HIF-1α/CP loop
Esquema
Vol 174
Artículo 116500- mai 2024 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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