3H-1,2-dithiole-3-thione protects retinal pigment epithelium cells against Ultra-violet radiation via activation of Akt-mTORC1-dependent Nrf2-HO-1 signaling

• DOI: 10.1038/srep25525
• Publication Date: 2016-05-06T09:07:13Z
• Authors: Ke-ran Li; Su-qing Yang; Yi-qing Gong; Hong Yang; Xiu-miao Li; Yu-xia Zhao; Jin Yao; Qin Jiang; Cong Cao
• Keywords: 0303 health sciences; NF-E2-Related Factor 2; Ultraviolet Rays; Membrane Proteins; Thiones; Apoptosis; Radiation-Protective Agents; Retinal Pigment Epithelium; Thiophenes; Mechanistic Target of Rapamycin Complex 1; Article; Mice, Inbred C57BL; 03 medical and health sciences; Animals; Humans; Reactive Oxygen Species; Proto-Oncogene Proteins c-akt; Cells, Cultured; Heme Oxygenase-1; Signal Transduction

Excessive UV radiation and reactive oxygen species (ROS) cause retinal pigment epithelium (RPE) cell injuries. Nrf2 regulates transcriptional activation of many anti-oxidant genes. Here, we tested the potential role 3H-1,2-dithiole-3-thione (D3T) against or ROS damages in cultured RPE cells (both primary ARPE-19 line). We showed that D3T significantly inhibited UV-/H2O2-induced death apoptosis. UV-stimulated production was dramatically by pretreatment. induced phosphorylation cells, causing disassociation with KEAP1 its subsequent nuclear accumulation. This led to expression antioxidant response elements (ARE)-dependent gene heme oxygenase-1 (HO-1). Nrf2-HO-1 required for D3T-mediated cytoprotective effect. shRNA knockdown S40T dominant negative mutation as well HO-1 inhibitor Zinc protoporphyrin (ZnPP) largely D3T's effects radiation. Yet, exogenous overexpression enhanced activity cells. Further studies activated Akt/mTORC1 Akt-mTORC1 inhibitors, Akt1 shRNA, not only D3T-induced activation, but also abolished effects. In vivo, intravitreal injection protected from light-induced dysfunctions mice. Thus, protects UV-induced via Akt-mTORC1-Nrf2-HO-1 signaling axis.