当前位置：
X-MOL 学术
›
Drug Des. Dev. Ther.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
L-Cysteine Provides Neuroprotection of Hypoxia-Ischemia Injury in Neonatal Mice via a PI3K/Akt-Dependent Mechanism
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2021-02-11 , DOI: 10.2147/dddt.s293025 Tingting Li 1 , Jiangbing Li 1, 2 , Tong Li 3 , Yijing Zhao 1 , Hongfei Ke 1 , Shuanglian Wang 1 , Dexiang Liu 4 , Zhen Wang 1
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2021-02-11 , DOI: 10.2147/dddt.s293025 Tingting Li 1 , Jiangbing Li 1, 2 , Tong Li 3 , Yijing Zhao 1 , Hongfei Ke 1 , Shuanglian Wang 1 , Dexiang Liu 4 , Zhen Wang 1
Affiliation
Background: Previous work within our laboratory has revealed that hydrogen sulfide (H2S) can serve as neuroprotectant against brain damage caused by hypoxia-ischemia (HI) exposure in neonatal mice. After HI insult, activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has been shown to be implicated in neuro-restoration processes. The goal of the current study was to determine whether the neuroprotective effects of H2S were mediated by the PI3K/Akt signaling pathway.
Methods: The mouse HI model was built at postnatal day 7 (P7), and the effects of L-Cysteine treatment on acute brain damage (72 h post-HI) and long-term neurological responses (28 days post-HI) were evaluated. Nissl staining and Transmission electron microscopy were used to evaluate the neuronal loss and apoptosis. Immunofluorescence imaging and dihydroethidium staining were utilized to determine glial cell activation and ROS content, respectively.
Results: Quantitative results revealed that L-Cysteine treatment significantly prevented the acute effects of HI on apoptosis, glial cell activation and oxidative injury as well as the long-term effects upon memory impairment in neonatal mice. This protective effect of L-Cysteine was found to be associated with the phosphorylation of Akt and phosphatase and a tensin homolog deletion on chromosome 10 (PTEN). Following treatment with the PI3K inhibitor, LY294002, the neuroprotective effects of L-Cysteine were attenuated.
Conclusion: PTEN/PI3K/Akt signaling was involved in mediating the neuroprotective effects of exogenous H2S against HI exposure in neonatal mice.
中文翻译：
L-半胱氨酸通过 PI3K/Akt 依赖机制对新生小鼠缺氧缺血损伤提供神经保护
背景：我们实验室以前的工作表明，硫化氢 (H 2 S) 可以作为新生小鼠因缺氧缺血 (HI) 暴露引起的脑损伤的神经保护剂。HI 损伤后，已显示磷脂酰肌醇-3-激酶 (PI3K)/蛋白激酶 B (Akt) 信号通路的激活与神经恢复过程有关。本研究的目的是确定 H 2 S 的神经保护作用是否由 PI3K/Akt 信号通路介导。
方法：小鼠 HI 模型在出生后第 7 天（P7）建立，评估 L-半胱氨酸治疗对急性脑损伤（HI 后 72 小时）和长期神经系统反应（HI 后 28 天）的影响。Nissl染色和透射电子显微镜用于评估神经元损失和细胞凋亡。免疫荧光成像和二氢乙锭染色分别用于确定胶质细胞活化和 ROS 含量。
结果：定量结果显示，L-半胱氨酸治疗显着阻止了 HI 对细胞凋亡、神经胶质细胞活化和氧化损伤的急性影响，以及对新生小鼠记忆障碍的长期影响。发现 L-半胱氨酸的这种保护作用与 Akt 和磷酸酶的磷酸化以及 10 号染色体 (PTEN) 上的张力蛋白同源物缺失有关。用 PI3K 抑制剂 LY294002 治疗后，L-半胱氨酸的神经保护作用减弱。
结论： PTEN/PI3K/Akt 信号通路参与介导外源 H 2 S 对新生小鼠 HI 暴露的神经保护作用。
更新日期：2021-04-20
Methods: The mouse HI model was built at postnatal day 7 (P7), and the effects of L-Cysteine treatment on acute brain damage (72 h post-HI) and long-term neurological responses (28 days post-HI) were evaluated. Nissl staining and Transmission electron microscopy were used to evaluate the neuronal loss and apoptosis. Immunofluorescence imaging and dihydroethidium staining were utilized to determine glial cell activation and ROS content, respectively.
Results: Quantitative results revealed that L-Cysteine treatment significantly prevented the acute effects of HI on apoptosis, glial cell activation and oxidative injury as well as the long-term effects upon memory impairment in neonatal mice. This protective effect of L-Cysteine was found to be associated with the phosphorylation of Akt and phosphatase and a tensin homolog deletion on chromosome 10 (PTEN). Following treatment with the PI3K inhibitor, LY294002, the neuroprotective effects of L-Cysteine were attenuated.
Conclusion: PTEN/PI3K/Akt signaling was involved in mediating the neuroprotective effects of exogenous H2S against HI exposure in neonatal mice.
中文翻译：
L-半胱氨酸通过 PI3K/Akt 依赖机制对新生小鼠缺氧缺血损伤提供神经保护
背景：我们实验室以前的工作表明，硫化氢 (H 2 S) 可以作为新生小鼠因缺氧缺血 (HI) 暴露引起的脑损伤的神经保护剂。HI 损伤后，已显示磷脂酰肌醇-3-激酶 (PI3K)/蛋白激酶 B (Akt) 信号通路的激活与神经恢复过程有关。本研究的目的是确定 H 2 S 的神经保护作用是否由 PI3K/Akt 信号通路介导。
方法：小鼠 HI 模型在出生后第 7 天（P7）建立，评估 L-半胱氨酸治疗对急性脑损伤（HI 后 72 小时）和长期神经系统反应（HI 后 28 天）的影响。Nissl染色和透射电子显微镜用于评估神经元损失和细胞凋亡。免疫荧光成像和二氢乙锭染色分别用于确定胶质细胞活化和 ROS 含量。
结果：定量结果显示，L-半胱氨酸治疗显着阻止了 HI 对细胞凋亡、神经胶质细胞活化和氧化损伤的急性影响，以及对新生小鼠记忆障碍的长期影响。发现 L-半胱氨酸的这种保护作用与 Akt 和磷酸酶的磷酸化以及 10 号染色体 (PTEN) 上的张力蛋白同源物缺失有关。用 PI3K 抑制剂 LY294002 治疗后，L-半胱氨酸的神经保护作用减弱。
结论： PTEN/PI3K/Akt 信号通路参与介导外源 H 2 S 对新生小鼠 HI 暴露的神经保护作用。
京公网安备 11010802027423号