College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China.
Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-si, Jeonbuk, 56216, Republic of Korea.
Mol Biol Rep. 2024 May 5;51(1):607. doi: 10.1007/s11033-024-09568-5.
Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation.
Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis.
Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.
脑出血（ICH）是一种严重的神经疾病，治疗选择有限，其中继发性免疫反应和特定的细胞死亡形式，如细胞焦亡，会加重脑损伤。细胞焦亡涉及gasdermin 介导的膜孔，增加炎症和神经损伤，其中 NLRP3/Caspase-1/GSDMD 途径是这一过程的核心。过氧化物还原酶 II（Prx II）因其具有线粒体保护和清除活性氧（ROS）的能力而备受关注，似乎是一种有前途的神经元细胞焦亡调节剂。然而，其确切作用和作用机制需要更明确的定义。本研究旨在探讨 Prx II 对神经元细胞焦亡的影响及其机制，特别是关于内质网（ER）应激和氧化应激诱导的神经元损伤调节。
利用 MTT 测定法、显微镜观察、Hoechst/PI 染色、Western blot 和免疫荧光法，我们发现 Prx II 能有效减轻 LPS/ATP 诱导的 HT22 海马神经元细胞的细胞焦亡和神经炎症。我们的结果表明，Prx II 的神经保护作用是通过激活 PI3K/AKT 和抑制 ER 应激途径介导的，通过减少线粒体功能障碍和 ROS/MAPK/NF-κB 途径减少神经元细胞焦亡。这些发现强调了 Prx II 通过调节参与神经元细胞焦亡的关键信号通路，减轻继发性脑损伤，从而在改善脑出血结果方面具有潜在的治疗价值。
本研究不仅强调了 Prx II 在神经保护中的重要性，还为脑出血的治疗提供了新的干预途径，强调了氧化还原调节、ER 应激和线粒体动力学在神经炎症和细胞死亡管理中的复杂相互作用。
