ROS ingestion by RPE cells is turned off by increased protein kinase C activity and by increased calcium.
The activation of protein kinase C (PKC) by phorbol myristate acetate (PMA) rapidly inhibits the phagocytosis of rod outer segments (ROS) by cultured rat retinal pigment epithelial (RPE) cells. PMA, at a concentration between 3.3 and 10 nM, blocks ROS ingestion by 50%, but does not inhibit the binding of ROS. The Ca2+ ionophore, A23187, also inhibits ROS phagocytosis, with an IC50 of about 0.5-1.0 microM and interferes with the ability of RPE cells to bind ROS. The effects of both of these drugs are reversible after drug washout. When PMA and A23187 are applied to cells consecutively, the effects are additive. These results suggest either that PMA and A23187, act upon the same proteins in the pathway which controls ROS ingestion, or that A23187 affects phagocytosis at the ROS binding level, while PKC affects steps further along the ingestion path. The effect of this process is to shut down the ingestion of ROS, as is seen during the prolonged feeding of ROS to RPE cells in culture.
Hall
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Jules Stein Eye Institute, UCLA Medical Centre 90024-7008.
Abrams
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Mittag
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D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D046508:Culture Techniques; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012374:Rod Cell Outer Segment / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010703:Phorbol Esters; C008876:phorbol-12,13-didecanoate; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium