Implication of protein carboxymethylation in retinal pigment epithelial cell chemotaxis.
Two chemoattractants for retinal pigment epithelial (RPE) cells, fibronectin (FN) and platelet-derived growth factor (PDGF) were found to enhance protein carboxymethylation mediated by S-adenosyl-L-methionine in RPE cells measured by [3H]methanol hydrolyzed from TCA precipitable protein methyl esters labelled with [3H]methionine. The effect was rapid, peaking at 2 min when [3H]methanol production was enhanced 120% by FN and 150% by PDGF. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 10 microM), adenosine (100 microM), and L-homocysteine thiolactone (100 microM) inhibited FN-induced carboxymethylation by 60%, and PDGF-induced carboxymethylation by 59%. In modified Boyden chamber assays, the combination of EHNA (10 microM), adenosine (100 microM), and L-homocysteine thiolactone (100 microM) markedly inhibited FN-induced chemotaxis by 88% and PDGF-induced chemotaxis by 93%). Migration of RPE cells has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR). Inhibition of protein carboxymethylation may provide a new target in the development of pharmacologic therapy for PVR.
Hackett
S F
SF
Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville.
Campochiaro
P A
PA
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D002633:Chemotaxis; D005136:Eye Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D000432:Methanol / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011496:Protein Methyltransferases / Q000378:metabolism*; D011497:Protein O-Methyltransferase / Q000378:metabolism*
D005136:Eye Proteins; D005353:Fibronectins; D010982:Platelet-Derived Growth Factor; D006710:Homocysteine; C010192:9-(2-hydroxy-3-nonyl)adenine; C007957:homocysteine thiolactone; D011496:Protein Methyltransferases; D011497:Protein O-Methyltransferase; D000225:Adenine; D000241:Adenosine; D000432:Methanol