https://scholars.lib.ntu.edu.tw/handle/123456789/416953
Title: | Activation of mitogen-activated protein kinases is essential for hydrogen peroxide -induced apoptosis in retinal pigment epithelial cells | Authors: | Ho T.-C. Yang Y.-C. Cheng H.-C. Wu A.-C. SHOW-LI CHEN Chen H.-K. Tsao Y.-P. |
Keywords: | AIF; Hydrogen peroxide; JNK; p38; Rac1; RPE | Issue Date: | 2006 | Journal Volume: | 11 | Journal Issue: | 11 | Start page/Pages: | 1899-1908 | Source: | Apoptosis | Abstract: | Retinal 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-33750622313&doi=10.1007%2fs10495-006-9403-6&partnerID=40&md5=39e4195f75fd4c36d108f95cbc155633 https://scholars.lib.ntu.edu.tw/handle/123456789/416953 |
ISSN: | 1360-8185 | DOI: | 10.1007/s10495-006-9403-6 | SDG/Keyword: | apoptosis 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 difficile |
Appears in Collections: | 微生物學科所 |
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