PRDX6 attenuates oxidative stress- and TGFbeta-induced abnormalities of human trabecular meshwork cells.
Oxidative stress and TGFbeta-induced disturbance of cells and tissues are implicated in initiation and progression of pathophysiology of cells/tissues. Using primary human trabecular meshwork (TM) cells from normal and glaucomatous subjects, this study demonstrated that peroxiredoxin (PRDX) 6, an antioxidant, offsets the deleterious effects of oxidative stress on TM cells by optimizing ROS and TGFbeta levels. An analysis of glaucomatous TM cells revealed a reduced expression of PRDX6 mRNA and protein. Biochemical assays disclosed enhanced levels of ROS, as well as high levels of TGFbetas and these cells expressed elevated extracellular matrix (ECM) and Tsp1 proteins with reduced MMP2; conditions implicated in the pathophysiology of glaucoma. Non-glaucomatous TM cells exposed to TGFbetas/ROS showed similar features as in glaucomatous cells. The abnormalities induced were reversed by delivery of PRDX6. The data provide evidence that oxidative stress-induced abnormality in TM may be related to reduced PRDX6 expression and provide a foundation for antioxidant-based therapeutics for treating glaucoma.
Fatma
Nigar
N
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Kubo
Eri
E
Toris
Carol B
CB
Stamer
W D
WD
Camras
Carl B
CB
Singh
Dhirendra P
DP
D000199:Actins / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism; D014335:Tropomyosin / Q000378:metabolism; D000099222:betaIG-H3 Protein
D000199:Actins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019204:GTP-Binding Proteins; D006861:Hydrogen Peroxide; D020778:Matrix Metalloproteinase 2; D016877:Oxidants; D054465:Peroxiredoxin VI; D017395:Plasminogen Activator Inhibitor 1; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D011503:Transglutaminases; D014335:Tropomyosin; D000099222:betaIG-H3 Protein; C051321:SERPINE1 protein, human; C490775:TPM1 protein, human; C518659:TPM2 protein, human; C515977:PRDX6 protein, human; C522361:MMP2 protein, human