Angiotensin II type 1 receptor blockade suppresses H2O2-induced retinal degeneration in photoreceptor cells

作者：Yin Yuan; Huang Shi Wei^*; Zheng Ya Juan; Dong Ya Ru

来源：Cutaneous and Ocular Toxicology, 2015, 34(4): 307-312.

DOI：10.3109/15569527.2014.979427

• 661 W cell
• apoptosis
• AT1R blockers
• H2O2
• oxidative stress
• retina

Exposure to reactive oxygen species (ROS) leads to the development and progression of retinal degenerative diseases. However, the exact mechanisms are not fully understood. In this article, the role of angiotensin II type 1 receptor (AT1R) signaling in H2O2-induced retinal damage was examined. Mouse photoreceptor-derived 661W cells were treated with the AT1R blockers valsartan, losartan and candesartan before exposure to H2O2. Cell viability, intracellular ROS level, mitochondrial membrane potential (MMP), cytochrome-c level, DNA fragmentation, caspase activity and gene expression were detected. Pre-treatment of 661W cells with AT1R blockers significantly decreased H2O2-mediated toxicity and reduced the ROS level. In addition, apoptosis-related biochemical indicators showed that pre-incubation of AT1R blockers would elevate the MMP, decrease the release of cytochrome-c and formation of DNA fragmentation, and inhibit activities of caspase-3 and caspase-9 in exogenous H2O2-treated 661W cells. Moreover, treatment with AT1R blockers suppressed the expression of Egr1, Fosl1 and Lox12. These results suggest that AT1R signaling mediates H2O2-induced apoptosis, at least partially through generating the ROS and increasing the levels of proapoptotic molecules in 661 W cells. AT1R blockade may provide a new therapeutic approach for preventing oxidative stress-induced retinal neural damage.

• 出版日期2015
• 单位吉林大学