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Heliox Protects SH-SY5Y Cells from Oxygen-Glucose Deprivation/Reperfusion-Induced Ferroptosis.
Yu, Shuai; Xiong, Wei; Xu, Wanjing; Chen, Yafen.
Afiliación
  • Yu S; Department of Anesthesiology, Zhongshan Hospital, Xiamen University, 361004 Xiamen, China.
  • Xiong W; Department of Anesthesiology, Zhongshan Hospital, Xiamen University, 361004 Xiamen, China.
  • Xu W; Department of Anesthesiology, Zhongshan Hospital, Xiamen University, 361004 Xiamen, China.
  • Chen Y; Department of Anesthesiology, Zhongshan Hospital, Xiamen University, 361004 Xiamen, China.
J Integr Neurosci ; 23(1): 14, 2024 Jan 16.
Article en En | MEDLINE | ID: mdl-38287843
ABSTRACT

BACKGROUND:

Heliox shows protective effects against acute focal ischemia-reperfusion injury in the brain. However, further research is needed to unveil the intricate molecular mechanisms involved. Determining how heliox affects ferroptosis caused by oxygen-glucose deprivation/reoxygenation (OGD/R) in SH-SY5Y cells as well as the underlying mechanism was the goal of the current work.

METHODS:

With the use of 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA), JC-1, and methyl thiazolyl tetrazolium, we assessed the survival, reactive oxygen species (ROS), and mitochondrial membrane potential in SH-SY5Y cells after they had been exposed to OGD/R and heliox. The expression of molecules associated with ferroptosis and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed using quantitative polymerase chain reaction (PCR) and immunoblotting, while malondialdehyde (MDA), oxidized glutathione disulfide (GSSG), ferrous ion (Fe2+), and reduced glutathione (GSH) levels were evaluated using biochemical kits.

RESULTS:

OGD/R treatment reduced the GSH to GSSG ratio; the potential of the mitochondrial membrane; the expression of the proteins GSH, SLC7A11, and glutathione peroxidase 4 (GPX4); and the ability of SH-SY5Y cells to survive. In contrast, OGD/R treatment increased the expression of cyclooxygenase-2 (COX2), ACSL4, and ferritin heavy chain 1 (FTH1) proteins, the production of MDA and GSSG, and the levels of ROS and Fe2+. However, heliox effectively mitigated all these OGD/R-induced effects. Furthermore, in OGD/R-treated SH-SY5Y cells, heliox administration stimulated the PI3K/AKT pathway while suppressing the nuclear factor-κB (NF-κB) pathway. When MK-2206, an AKT inhibitor, was applied concurrently to the cells, these outcomes were reversed.

CONCLUSIONS:

Heliox prevents OGD/R from causing ferroptosis in SH-SY5Y cells by activating the PI3K/AKT pathway. This suggests a promising therapeutic potential for heliox use in the management of ischemia/reperfusion injury.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Ferroptosis / Helio / Neuroblastoma Límite: Humans Idioma: En Revista: J Integr Neurosci Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Singapur

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Ferroptosis / Helio / Neuroblastoma Límite: Humans Idioma: En Revista: J Integr Neurosci Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Singapur