Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea; Department of Medical Science Konkuk University School of Medicine, Konkuk University, Seoul, Republic of Korea.
Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):3011-3016. doi: 10.1016/j.bbrc.2018.08.086. Epub 2018 Aug 22.
Astrocytes perform a variety of functions that are important for normal neuronal activity and recovery after brain injury. Because astrocytes are very vulnerable to HO, protection of astrocytes from oxidative damage in various neurological diseases is important in maintaining brain function and preventing brain damage. In this study, we investigated the characteristics and mechanisms of a specific imidazoline I2 receptor agonist 2-BFI-mediated cytoprotection using a rat astrocyte cultures of HO-exposed oxidative stress. Here we show that 2-BFI in HO-exposed astrocytes protects cell death through increased lysosomal membrane stability, LC3-II conversion, and subsequently suppresses accumulation of p62. These effects of 2-BFI were significantly reversed after treatment with the lysozyme activity inhibitor Bafilomycin A1. These results suggest that the cytoprotective effects of 2-BFI, which increases lysosomal stability in oxidative stress, may involve regulation of lysosomal-associated membrane protein-dependent autophagy and autolysosome degradation in astrocytes.
星形胶质细胞发挥多种功能，对于正常神经元活动和脑损伤后恢复至关重要。由于星形胶质细胞对羟自由基（HO）非常敏感，因此在各种神经疾病中保护星形胶质细胞免受氧化损伤对于维持脑功能和防止脑损伤非常重要。在这项研究中，我们使用暴露于羟自由基的大鼠星形胶质细胞培养物研究了特定咪唑啉 I2 受体激动剂 2-BFI 介导的细胞保护的特性和机制。在这里，我们表明 2-BFI 可通过增加溶酶体膜稳定性、LC3-II 转化来保护 HO 暴露的星形胶质细胞中的细胞死亡，随后抑制 p62 的积累。用溶酶体酶抑制剂巴弗洛霉素 A1 处理后，2-BFI 的这些作用明显逆转。这些结果表明，2-BFI 通过增加氧化应激下的溶酶体稳定性发挥细胞保护作用，可能涉及调节星形胶质细胞中溶酶体相关膜蛋白依赖性自噬和自噬溶酶体降解。
