title: Angiotensin II type 1 receptor blockade suppresses H2O2-induced retinal degeneration in photoreceptor cells.
abstract: 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 H(2)O(2)-induced retinal damage was examined. Mouse photoreceptor-derived 661 W cells were treated with the AT1R blockers valsartan, losartan and candesartan before exposure to H(2)O(2). Cell viability, intracellular ROS level, mitochondrial membrane potential (MMP), cytochrome-c level, DNA fragmentation, caspase activity and gene expression were detected. Pre-treatment of 661 W cells with AT1R blockers significantly decreased H(2)O(2)-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 H(2)O(2)-treated 661 W cells. Moreover, treatment with AT1R blockers suppressed the expression of Egr1, Fosl1 and Lox12. These results suggest that AT1R signaling mediates H(2)O(2)-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.
authors.affiliation: a The Second Hospital of Jilin University , Changchun , Jilin , China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yin
authors.affiliation: a The Second Hospital of Jilin University , Changchun , Jilin , China.
authors.forename: Shi-Wei
authors.initials: SW
authors.lastname: Huang
authors.affiliation: a The Second Hospital of Jilin University , Changchun , Jilin , China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Zheng
authors.affiliation: a The Second Hospital of Jilin University , Changchun , Jilin , China.
authors.forename: Ya-Ru
authors.initials: YR
authors.lastname: Dong
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D045304:Cytochromes c / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012162:Retinal Degeneration / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D020169:Caspases
keywords: 661 W cell; AT1R blockers; H2O2; apoptosis; oxidative stress; retina