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Omar Shoukfeh, Chanping Liang, Marlyn P Langford; Differential effect of prostaglandins on γ-glutamyltranspeptidase activity and glutamate/cystine uptake in trabecular meshwork cells.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4692.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effects of prostaglandin (PG) treatment on γ-glutamyltranspeptidase (GGT; plays key extracellular role in recapture of Cys for glutathione synthesis) activity and glutamate (Glu) and cystine (Cys) uptake in trabecular meshwork cells (TMC).
The effect of PG treatment on TMC GGT activity was determined by standard GGT assay utilizing conversion of γ-glutamyl p-nitroanilide in the presence of glycyl-gylcine with or without acivicin (AT125, GGT inhibitor). The Na+-independent uptake of radiolabeled Cys and Glu by Xc- antiporter was determined in replicate TMC cultures treated with different concentrations of PG A2, D2, F1 and F2.
TMC GGT activity was inhibited 50±16% by 10-300 ng/mL PGF1 and AT125. GGT activity was inhibited 23-41% by 1 ug/mL of PGA2, D2 or F2. Concomitantly, PGA2, and PGF1 treatment of TMC did not significantly affect Na+-independent uptake of radiolabeled Glu or Cys. However, PGD2 increased Na+-independent radiolabeled Glu uptake by 39±11%, but not Cys uptake (<2.5%). In contrast, PGF2 treatment induced a dose-dependent decrease in TMC Na+-independent radiolabeled Glu uptake (up to 37±9%) and radiolabeled Cys uptake (up to 12±7%).
TMC GGT and Xc- antiporter activity can be modulated by prostaglandins. The results suggest that endogenous and exogenous prostaglandins may regulate TMC function in vivo via modulation of GGT and Xc- antiporter coordinated activities.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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