Peroxiredoxin 6 delivery attenuates TNF-alpha-and glutamate-induced retinal ganglion cell death by limiting ROS levels and maintaining Ca2+ homeostasis.
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-alpha in the RGCs' local microenvironment. Herein we show that the transduction of Peroxiredoxin 6 (PRDX6) attenuates TNF-alpha- 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-alpha displayed elevated levels of ROS and reduced expression of PRDX6, and underwent apoptosis. A supply of PRDX6 protected RGCs from glutamate and TNF-alpha induced cytotoxicity by reducing ROS level and NF-kappaB 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.
Fatma
Nigar
N
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Kubo
E
E
Sen
M
M
Agarwal
N
N
Thoreson
W B
WB
Camras
C B
CB
Singh
D P
DP
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D054465:Peroxiredoxin VI; D002118:Calcium