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Abstract #21890 Published in IGR 10-4
Peroxiredoxin 6 delivery attenuates TNF-α-and glutamate-induced retinal ganglion cell death by limiting ROS levels and maintaining Ca2+ homeostasis
Fatma N; Kubo E; Sen M; Agarwal N; Thoreson WB; Camras CB; Singh DPBrain Research 2008; 1233: 63-78
Higher expression of reactive oxygen species (ROS) is implicated in neurological disorders. A major event in glaucoma, the death of retinal ganglion cells (RGCs), has been associated with elevated levels of glutamate and TNF-α in the RGCs' local microenvironment. Herein we show that the transduction of Peroxiredoxin 6 (PRDX6) attenuates TNF-α- and glutamate-induced RGC death, by limiting ROS and maintaining Ca2+ homeostasis. Immunohistochemical staining of rat retina disclosed the presence of PRDX6 in RGCs, and Western and real-time PCR analysis revealed an abundance of PRDX6 protein and mRNA. RGCs treated with glutamate and/or TNF-α displayed elevated levels of ROS and reduced expression of PRDX6, and underwent apoptosis. A supply of PRDX6 protected RGCs from glutamate and TNF-α induced cytotoxicity by reducing ROS level and NF-(Κ)B activation, and limiting increased intracellular Ca2+ influx. Results provide a rationale for use of PRDX6 for blocking ROS-mediated pathophysiology in glaucoma and other neuronal disorders.
Dr. D.P. Singh, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA. dpsingh@unmc.edu
