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Photoreceptor phagocytosis selectively activates PPARγ expression in retinal pigment epithelial cells
Author(s) -
Ershov Alexey V.,
Bazan Nicolas G.
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000501)60:3<328::aid-jnr7>3.0.co;2-5
Subject(s) - phagocytosis , retinoic acid , biology , microbiology and biotechnology , peroxisome proliferator activated receptor , receptor , retinal pigment epithelium , cycloheximide , cell culture , retinal , biochemistry , genetics
Phagocytosis of tips of rod outer segments (ROS) by retinal pigment epithelial (RPE) cells is vitally important for maintaining structural and functional integrity of the retina. We previously reported that receptor‐mediated specific phagocytosis of ROS induces expression of early response genes coding for transcription factors. Here we study the expression of peroxisome proliferator‐activated receptors (PPAR) ‐α, ‐δ (β) and ‐γ during ROS phagocytosis of rat RPE cells in primary cell culture, using competitive quantitative RT‐PCR. During phagocytosis of ROS (but not of latex particles) by RPE cells, RT‐PCR revealed a transient increase in PPARγ mRNA expression, that peaked at 4–6 hr. We sequenced and described two alternatively spliced variants of rat PPARγ: rPPARγ1a and rPPARγ1b. Both of these, along with the recently described rPPARγ2 were induced by ROS phagocytosis. PPARα and PPARδ mRNA expression was also detected in RPE cells, but the level of expression did not change during ROS phagocytosis. All ‐ trans ‐retinoic acid and prostaglandin E 2 (PGE 2 ) selectively potentiated both basal and ROS‐phagocytosis‐induced PPARγ expression. All ‐ trans ‐retinoic acid had the opposite inhibitory effect on PPARα and PPARδ expression. Cycloheximide had a dual action on PPARγ expression in RPE cells: it enhanced expression under basal conditions but repressed expression induced by ROS phagocytosis. It also stimulated expression of PPARα but had no effect on PPARδ. Selective activation of PPARγ may play an important role in regulating the expression of target genes that are involved in lipid and fatty acid metabolism in the photoreceptor renewal process. J. Neurosci. Res. 60:328–337, 2000 © 2000 Wiley‐Liss, Inc.