Involvement of microRNA-34a in Age-Related Susceptibility to Oxidative Stress in ARPE-19 Cells by Targeting the Silent Mating Type Information Regulation 2 Homolog 1/p66shc Pathway: Implications for Age-Related Macular Degeneration.

摘要: The aging retinal pigment epithelium and oxidative stress, mediated by reactive oxygen species (ROS) accumulation, have been implicated in the mechanisms of age-related macular degeneration (AMD). expression level adapter protein p66shc, a key that regulates cellular is relatively low under normal conditions because effects silent mating type information regulation 2 homolog 1 (SIRT1) on binding fully deacetylated histone H3' to p66shc promoter region, thus inhibiting transcription expression. equilibrium between SIRT1 disrupted presence various stresses, including AMD. As major target gene, regulated microRNA-34a (miR-34a), overexpression miR-34a results significant inhibition post-transcriptional SIRT1. Furthermore, our recent studies demonstrated significantly upregulated, accompanied reduced tolerance stress hydrogen peroxide-induced prematurely senescent ARPE-19 cells. Moreover, decreased, whereas increased these Accordingly, may play role susceptibility cells targeting SIRT1/p66shc pathway, leading In this review article, we discuss functions modulating pathway conditions,