Roles of ¦Áv¦Â5, FAK and MerTK in oxidative stress inhibition of RPE cell phagocytosis

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• 作者：Suofu Qin ; ^{qin_suofu@allergan.com} ; Gerard A. Rodrigues
• 关键词：cathepsin D ; ¦ÁV¦Â5 ; FAK ; MerTK ; oxidative stress ; phagocytosis
• 刊名：Experimental Eye Research
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：94
• 期：1
• 页码：63-70
• 全文大小：683 K

文摘

Efficient phagocytosis of photoreceptor outer segments (POS) by retinal pigment epithelial cells (RPE) plays a key role in biological renewal of these highly peroxidizable structures and in maintenance of retina health. Here, we used an in?vitro RPE cell phagocytosis assay to investigate how sub-lethal oxidative stress modifies the key components of the cell phagocytic machinery leading to severe impairment of phagocytosis. Sub-lethal oxidative treatment, induced by hydrogen peroxide (H₂O₂), significantly inhibited binding and uptake of POS by RPE cells. However, sub-lethal oxidative stress did not affect cell surface expression of ¦Áv¦Â5 or RPE cell adhesion to ¦Áv¦Â5. Similarly, the enzymatic activity of mature cathepsin D was not altered upon challenge by oxidative stress. In contrast, studies of signaling molecules in the RPE cell phagocytic machinery revealed that sub-lethal oxidative stress inhibits POS-induced activation of FAK and MerTK. Our data demonstrate that sub-lethal oxidative treatment with H₂O₂ inhibits phagocytic activity of ARPE-19 cells, in part by inhibiting FAK and MerTK.