title: Peroxiredoxin 6 delivery attenuates TNF-alpha-and glutamate-induced retinal ganglion cell death by limiting ROS levels and maintaining Ca2+ homeostasis.
abstract: 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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Nigar
authors.initials: N
authors.lastname: Fatma
authors.forename: E
authors.initials: E
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Sen
authors.forename: N
authors.initials: N
authors.lastname: Agarwal
authors.forename: W B
authors.initials: WB
authors.lastname: Thoreson
authors.forename: C B
authors.initials: CB
authors.lastname: Camras
authors.forename: D P
authors.initials: DP
authors.lastname: Singh
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D054465:Peroxiredoxin VI; D002118:Calcium