Ho T.-C.Yang Y.-C.Cheng H.-C.Wu A.-C.SHOW-LI CHENChen H.-K.Tsao Y.-P.2019-08-302019-08-3020061360-8185https://www.scopus.com/inward/record.uri?eid=2-s2.0-33750622313&doi=10.1007%2fs10495-006-9403-6&partnerID=40&md5=39e4195f75fd4c36d108f95cbc155633https://scholars.lib.ntu.edu.tw/handle/123456789/416953Retinal pigment epithelial (RPE) cells are constantly exposed to oxidative injury while clearing byproducts of photoreceptor turnover, a circumstance thought to be responsible for degenerative retinal diseases. The mechanisms of hydrogen peroxide (H2O2)-induced apoptosis in RPE cells are not fully understood. We studied signal transduction mechanisms of H 2O2-induced apoptosis in the human RPE cell line ARPE-19. Activation of two stress kinases (JNK and p38) occurs during H2O 2 stimulation, and H2O2-mediated cell death was significantly reduced by their specific inhibition. Exposure to a lethal dose of H2O2 elicited Bax translocation to the mitochondria and release of apoptosis-inducing factor (AIF) from the mitochondria, both of which were abolished by either JNK- or p38-specific inhibitors. Both H 2O2-induced cell death and JNK/p38 phosphorylation were partially inhibited by C. difficile toxin B, inhibitor of Rho, Rac, and cdc42. Use of pull-down assays revealed that the small GTPase activated by H 2O2 is Rac1. This study is the first to demonstrate that H2O2 induces a Rac1/JNK1/p38 signaling cascade, and that JNK and p38 activation is important for H2O2-induced apoptosis as well as AIF/Bax translocation of RPE cells. ? 2006 Springer Science + Business Media, LLC.en-USAIF; Hydrogen peroxide; JNK; p38; Rac1; RPE[SDGs]SDG2[SDGs]SDG3apoptosis inducing factor; hydrogen peroxide; mitogen activated protein kinase p38; mitogen activated protein kinase p38 inhibitor; protein Bax; Rac1 protein; stress activated protein kinase; stress activated protein kinase inhibitor; toxin; apoptosis; article; cell death; controlled study; cytokine release; enzyme activation; enzyme phosphorylation; exposure; human; human cell; mitochondrion; pigment cell; pigment epithelium; priority journal; signal transduction; Active Transport, Cell Nucleus; Anthracenes; Apoptosis; Apoptosis Regulatory Proteins; Bacterial Proteins; Bacterial Toxins; Cell Line, Tumor; Cell Nucleus; Enzyme Inhibitors; Humans; Hydrogen Peroxide; Imidazoles; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 8; p38 Mitogen-Activated Protein Kinases; Pigment Epithelium of Eye; Protein Transport; Pyridines; rac1 GTP-Binding Protein; Clostridium difficilejournal article10.1007/s10495-006-9403-6169270232-s2.0-33750622313