Produit-Zengaffinen Nathalie, Favez Tatiana, Pournaras Constantin J, Schorderet Daniel F
Faculty of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland.
Department of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland.
Adv Exp Med Biol. 2016;854:677-83. doi: 10.1007/978-3-319-17121-0_90.
Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell death that paralleled increased activity of JNK and c-jun. 661W cells cultured in presence of the inhibitor of JNK (D-JNKi) were less sensitive to hypoxia-induced cell death. In vivo, elevation in intraocular pressure (IOP) in the rat promoted cell death that correlated with modulation of JNK activation. In vivo inhibition of JNK activation with D-JNKi resulted in a significant and sustained decrease in apoptosis in the ganglion cell layer, the inner nuclear layer and the photoreceptor layer. These results highlight the protective effect of D-JNKi in ischemia/reperfusion induced cell death of the retina.
丝裂原活化蛋白激酶（MAPKs）是与细胞存活和死亡相关的关键调节因子。在主要的MAPK类别中，c-jun氨基末端激酶（JNK）已被证明可介导与细胞凋亡相关的细胞应激反应。在体外，缺氧诱导661W细胞死亡显著增加，这与JNK和c-jun活性增加平行。在JNK抑制剂（D-JNKi）存在下培养的661W细胞对缺氧诱导的细胞死亡敏感性较低。在体内，大鼠眼内压（IOP）升高促进细胞死亡，这与JNK激活的调节相关。用D-JNKi在体内抑制JNK激活导致神经节细胞层、内核层和光感受器层的细胞凋亡显著且持续减少。这些结果突出了D-JNKi在缺血/再灌注诱导的视网膜细胞死亡中的保护作用。
