Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, 501 Jinjudaero, Jinju 52828, South Korea.
Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, 501 Jinjudaero, Jinju 52828, South Korea.
Neuroscience. 2023 Jun 15;521:166-181. doi: 10.1016/j.neuroscience.2023.04.028. Epub 2023 May 4.
Ischemic stroke is a neurological disorder that causes pathological changes by increasing oxidative stress. Retinoic acid is one of the metabolites of vitamin A. It regulates oxidative stress and exerts neuroprotective effects. Thioredoxin is a small redox protein with antioxidant activity. The aim of this study was to investigate whether retinoic acid modulates the expression of thioredoxin in ischemic brain injury. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) surgery and retinoic acid (5 mg/kg) or vehicle was administered to adult male rats for four days prior to surgery. MCAO induced neurological deficits and increased oxidative stress and retinoic acid attenuated these changes. Retinoic acid ameliorated the MCAO-induced decrease in thioredoxin expression. MCAO decreases the interaction between thioredoxin and apoptosis signal-regulating kinase 1 (ASK1), and retinoic acid treatment alleviates this decrease. Glutamate (5 mM) exposure induced cell death and decreased thioredoxin expression in cultured neurons. Retinoic acid treatment attenuated these changes in a dose-dependent manner. Retinoic acid prevented the decrease of bcl-2 expression and the increase of bax expression caused by glutamate exposure. Moreover, retinoic acid attenuated the increases in caspase-3, cleaved caspase-3, and cytochrome c in glutamate-exposed neurons. However, the mitigation effects of retinoic acid were lower in thioredoxin siRNA-transfected neurons than in non-transfected neurons. These results demonstrate that retinoic acid regulates oxidative stress and thioredoxin expression, maintains the interaction between thioredoxin and ASK1, and modulates apoptosis-associated proteins. Taken together, these results suggest that retinoic acid has neuroprotective effects by regulating thioredoxin expression and modulating apoptotic pathway.
脑缺血是一种神经紊乱疾病，通过增加氧化应激导致病理变化。维 A 酸是维生素 A 的一种代谢物。它可以调节氧化应激并发挥神经保护作用。硫氧还蛋白是一种具有抗氧化活性的小还原蛋白。本研究旨在探讨维 A 酸是否可以调节缺血性脑损伤中硫氧还蛋白的表达。通过大脑中动脉闭塞 (MCAO) 手术诱导脑缺血，成年雄性大鼠在手术前四天给予维 A 酸 (5mg/kg) 或载体处理。MCAO 诱导神经功能缺损，并增加氧化应激，而维 A 酸减轻了这些变化。维 A 酸改善了 MCAO 诱导的硫氧还蛋白表达降低。MCAO 降低了硫氧还蛋白与凋亡信号调节激酶 1 (ASK1) 的相互作用，而维 A 酸处理减轻了这种降低。谷氨酸 (5mM) 暴露诱导培养神经元细胞死亡和硫氧还蛋白表达降低，维 A 酸处理以剂量依赖的方式减轻了这些变化。维 A 酸防止了谷氨酸暴露引起的 bcl-2 表达降低和 bax 表达增加。此外，维 A 酸减轻了谷氨酸暴露神经元中 caspase-3、cleaved caspase-3 和细胞色素 c 的增加。然而，在硫氧还蛋白 siRNA 转染的神经元中，维 A 酸的缓解作用低于未转染的神经元。这些结果表明，维 A 酸通过调节氧化应激和硫氧还蛋白表达，维持硫氧还蛋白和 ASK1 之间的相互作用，并调节凋亡相关蛋白，从而发挥神经保护作用。总之，这些结果表明，维 A 酸通过调节硫氧还蛋白表达和调节凋亡途径发挥神经保护作用。
