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BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.
Liu, Nan; Li, Chen; Yan, Cong; Yan, Hao-Chen; Jin, Bing-Xuan; Yang, Hong-Rui; Jiang, Guang-You; Gong, Hai-Dong; Li, Ji-Yi; Ma, Sheng-Ji; Liu, Huai-Lei; Gao, Cheng.
Affiliation
  • Liu N; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Li C; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Yan C; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Yan HC; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Jin BX; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Yang HR; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Jiang GY; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Gong HD; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Li JY; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Ma SJ; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Liu HL; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
  • Gao C; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, Chi
Free Radic Biol Med ; 222: 173-186, 2024 Jun 11.
Article in En | MEDLINE | ID: mdl-38871197
ABSTRACT
Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Free Radic Biol Med Year: 2024 Document type: Article
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Free Radic Biol Med Year: 2024 Document type: Article