α-Melanocyte-Stimulating Hormone Protects Retinal Vascular Endothelial Cells from Oxidative Stress and Apoptosis in a Rat Model of Diabetes

• DOI: 10.1371/journal.pone.0093433
• Publication Date: 2014-04-02T23:18:01Z
• Authors: Lijuan Zhang; Lijie Dong; Xun Liu; Yuanfeng Jiang; Lingjun Zhang; Xiaomin Zhang; Xiaorong Li; Yan Zhang
• Keywords: Terminal deoxynucleotidyl transferase

Aims Oxidative stress and apoptosis are among the earliest lesions of diabetic retinopathy. This study sought to examine anti-oxidative anti-apoptotic effects α-melanocyte-stimulating hormone (α-MSH) in early retinas explore underlying mechanisms retinal vascular endothelial cells. Methods Sprague-Dawley rats were injected intravenously with streptozocin induce diabetes. The intravitreally α-MSH or saline. At week 5 after diabetes, analyzed for reactive oxygen species (ROS) gene expression. One later, processed terminal deoxynucleotidyl transferase dUTP nick-end labeling staining transmission electron microscopy. Retinal cells stimulated by high glucose (HG) without α-MSH. expression Forkhead box O genes (Foxos) was examined through real-time PCR. Foxo4 overexpressed transient transfection prior HG treatment, oxidative CM-H2DCFDA annexin-V assays, respectively. Results In retinas, levels H2O2 ROS total anti-oxidant capacity normalized, apoptotic cell number reduced, ultrastructural injuries ameliorated Treatment also corrected aberrant changes eNOS, iNOS, ICAM-1, TNF-α retinas. Furthermore, inhibited up-regulation exposed HG, whereas overexpression abrogated HG-stimulated Conclusions normalized stress, reduced injuries, protective may be mediated inhibition induced HG. suggests an α-MSH-mediated potential intervention approach retinopathy a novel regulatory mechanism involving Foxo4.