Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAH
(1) SAH induces cellular stress and endoplasmic reticulum stress, activating the unfolded protein response (UPR) in nerve cells. IRE1 (inositol-requiring enzyme 1) is a protein that plays a critical role in cellular stress response. Its final product, Xbp1s, is essential for adapting to changes in t...
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MDPI AG
2023-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/5/1259 |
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| author | Kefan Wu Lili Chen Zhen Qiu Bo Zhao Jiabao Hou Shaoqin Lei Meng Jiang Zhongyuan Xia |
| author_facet | Kefan Wu Lili Chen Zhen Qiu Bo Zhao Jiabao Hou Shaoqin Lei Meng Jiang Zhongyuan Xia |
| author_sort | Kefan Wu |
| collection | DOAJ |
| description | (1) SAH induces cellular stress and endoplasmic reticulum stress, activating the unfolded protein response (UPR) in nerve cells. IRE1 (inositol-requiring enzyme 1) is a protein that plays a critical role in cellular stress response. Its final product, Xbp1s, is essential for adapting to changes in the external environment. This process helps maintain proper cellular function in response to various stressors. O-GlcNAcylation, a means of protein modification, has been found to be involved in SAH pathophysiology. SAH can increase the acute O-GlcNAcylation level of nerve cells, which enhances the stress capacity of nerve cells. The GFAT1 enzyme regulates the level of O-GlcNAc modification in cells, which could be a potential target for neuroprotection in SAH. Investigating the IRE1/XBP1s/GFAT1 axis could offer a promising avenue for future research. (2) Methods: SAH was induced using a suture to perforate an artery in mice. HT22 cells with Xbp1 loss- and gain-of-function in neurons were generated. Thiamet-G was used to increase O-GlcNAcylation; (3) Results: Severe neuroinflammation caused by subarachnoid hemorrhage leads to extensive endoplasmic reticulum stress of nerve cells. Xbp1s, the final product of unfolded proteins induced by endoplasmic reticulum stress, can induce the expression of the hexosamine pathway rate limiting enzyme GFAT1, increase the level of O-GlcNAc modification of cells, and have a protective effect on neural cells; (4) Conclusions: The correlation between Xbp1s displayed by immunohistochemistry and O-GlcNAc modification suggests that the IRE1/XBP1 branch of unfolded protein reaction plays a key role in subarachnoid hemorrhage. IRE1/XBP1 branch is a new idea to regulate protein glycosylation modification, and provides a promising strategy for clinical perioperative prevention and treatment of subarachnoid hemorrhage. |
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| language | English |
| last_indexed | 2024-03-11T03:55:54Z |
| publishDate | 2023-04-01 |
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| series | Biomedicines |
| spelling | doaj.art-9aa32605bc03418bb15a741373b2e09e2023-11-18T00:34:22ZengMDPI AGBiomedicines2227-90592023-04-01115125910.3390/biomedicines11051259Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAHKefan Wu0Lili Chen1Zhen Qiu2Bo Zhao3Jiabao Hou4Shaoqin Lei5Meng Jiang6Zhongyuan Xia7Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430064, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430064, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430064, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430064, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430064, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430064, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430064, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430064, China(1) SAH induces cellular stress and endoplasmic reticulum stress, activating the unfolded protein response (UPR) in nerve cells. IRE1 (inositol-requiring enzyme 1) is a protein that plays a critical role in cellular stress response. Its final product, Xbp1s, is essential for adapting to changes in the external environment. This process helps maintain proper cellular function in response to various stressors. O-GlcNAcylation, a means of protein modification, has been found to be involved in SAH pathophysiology. SAH can increase the acute O-GlcNAcylation level of nerve cells, which enhances the stress capacity of nerve cells. The GFAT1 enzyme regulates the level of O-GlcNAc modification in cells, which could be a potential target for neuroprotection in SAH. Investigating the IRE1/XBP1s/GFAT1 axis could offer a promising avenue for future research. (2) Methods: SAH was induced using a suture to perforate an artery in mice. HT22 cells with Xbp1 loss- and gain-of-function in neurons were generated. Thiamet-G was used to increase O-GlcNAcylation; (3) Results: Severe neuroinflammation caused by subarachnoid hemorrhage leads to extensive endoplasmic reticulum stress of nerve cells. Xbp1s, the final product of unfolded proteins induced by endoplasmic reticulum stress, can induce the expression of the hexosamine pathway rate limiting enzyme GFAT1, increase the level of O-GlcNAc modification of cells, and have a protective effect on neural cells; (4) Conclusions: The correlation between Xbp1s displayed by immunohistochemistry and O-GlcNAc modification suggests that the IRE1/XBP1 branch of unfolded protein reaction plays a key role in subarachnoid hemorrhage. IRE1/XBP1 branch is a new idea to regulate protein glycosylation modification, and provides a promising strategy for clinical perioperative prevention and treatment of subarachnoid hemorrhage.https://www.mdpi.com/2227-9059/11/5/1259subarachnoid hemorrhageXbp1sO-GlcNAcHBP |
| spellingShingle | Kefan Wu Lili Chen Zhen Qiu Bo Zhao Jiabao Hou Shaoqin Lei Meng Jiang Zhongyuan Xia Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAH Biomedicines subarachnoid hemorrhage Xbp1s O-GlcNAc HBP |
| title | Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAH |
| title_full | Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAH |
| title_fullStr | Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAH |
| title_full_unstemmed | Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAH |
| title_short | Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAH |
| title_sort | protective effect and mechanism of xbp1s regulating hbp o glcnacylation through gfat1 on brain injury after sah |
| topic | subarachnoid hemorrhage Xbp1s O-GlcNAc HBP |
| url | https://www.mdpi.com/2227-9059/11/5/1259 |
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