Valproic Acid Inhibits Endoplasmic Reticulum Stress and Reduces Ferroptosis After Traumatic Brain Injury.

IF 2.3 4区医学 Q3 PHARMACOLOGY & PHARMACY Dose-Response Pub Date : 2024-12-02 eCollection Date: 2024-10-01 DOI:10.1177/15593258241303646

Jie Chen, Lei Li, Lei Huang, Chengyu Zhao, Zhanwei Ruan

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Abstract

Backgound: Traumatic brain injury (TBI) is a severe neurological disorders, which invloving complicated molecular mechanisms, such as endoplasmic reticulum (ER) stress and ferroptosis. , However, the mechanism underlying TBI remains unclear.

Objectives: The Objective was to determine the effect of VPA on ER stress and ferroptosis, and affirm the relationship between ER stress and ferroptosis. Methods: The expression levels of GRP78, ATF6, CHOP and GPX4 in brain tissues were detected via western blot, histological staining, and immunofluorescence. The effect of VPA on ER stress and ferroptosis on OS cellswas evaluated in vitro and in vivo.

Results: In our study, we found that VPA suppressed ER stress after TBI by inhibiting the GRP78-ATF6-CHOP signaling pathway, which ameliorated ferroptosis by reversing the reduction of the ferroptosis protein GPX4. Furthermore, tissue defects, bleeding, and iron accumulation also reduced. Moreover, 4-phenylbutyric acid was used to further confirm our assumption.

Conclusion: VPA plays a neuroprotective role by inhibiting ER stress levels and subsequently inhibiting ferroptosis.

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丙戊酸抑制内质网应激和减少外伤性脑损伤后铁下垂。

背景：外伤性脑损伤（Traumatic brain injury， TBI）是一种严重的神经系统疾病，涉及内质网应激、铁下垂等复杂的分子机制。然而，TBI的发病机制尚不清楚。目的：观察VPA对内质网应激和铁下垂的影响，确定内质网应激与铁下垂的关系。方法：采用western blot、组织学染色、免疫荧光法检测大鼠脑组织中GRP78、ATF6、CHOP、GPX4的表达水平。体外和体内观察VPA对OS细胞内质网应激和铁下垂的影响。结果：在我们的研究中，我们发现VPA通过抑制GRP78-ATF6-CHOP信号通路抑制TBI后内质网应激，通过逆转铁下垂蛋白GPX4的减少来改善铁下垂。此外，组织缺损、出血和铁积累也有所减少。此外，4-苯基丁酸进一步证实了我们的假设。结论：VPA通过抑制内质网应激水平，进而抑制铁下垂，具有一定的神经保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Dose-Response PHARMACOLOGY & PHARMACY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

CiteScore

4.90

自引率

4.00%

发文量

140

审稿时长

>12 weeks

期刊介绍： Dose-Response is an open access peer-reviewed online journal publishing original findings and commentaries on the occurrence of dose-response relationships across a broad range of disciplines. Particular interest focuses on experimental evidence providing mechanistic understanding of nonlinear dose-response relationships.