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-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-κB 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 63-78 |
| Number of pages | 16 |
| Journal | Brain Research |
| Volume | 1233 |
| DOIs | |
| State | Published - Oct 3 2008 |
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Keywords
- Oxidative stress
- PRDX6
- Reactive oxygen species
- Retinal ganglion cell
- TNF-α
ASJC Scopus subject areas
- Neuroscience(all)
- Molecular Biology
- Clinical Neurology
- Developmental Biology
Cite this
Peroxiredoxin 6 delivery attenuates TNF-α-and glutamate-induced retinal ganglion cell death by limiting ROS levels and maintaining Ca2+ homeostasis. / Fatma, Nigar; Kubo, E.; Sen, M.; Agarwal, N.; Thoreson, Wallace B; Camras, C. B.; Singh, Dhirendra P.
In: Brain Research, Vol. 1233, 03.10.2008, p. 63-78.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Peroxiredoxin 6 delivery attenuates TNF-α-and glutamate-induced retinal ganglion cell death by limiting ROS levels and maintaining Ca2+ homeostasis
AU - Fatma, Nigar
AU - Kubo, E.
AU - Sen, M.
AU - Agarwal, N.
AU - Thoreson, Wallace B
AU - Camras, C. B.
AU - Singh, Dhirendra P
PY - 2008/10/3
Y1 - 2008/10/3
N2 - 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-κB 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.
AB - 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-κB 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.
KW - Oxidative stress
KW - PRDX6
KW - Reactive oxygen species
KW - Retinal ganglion cell
KW - TNF-α
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UR - http://www.scopus.com/inward/citedby.url?scp=51449113042&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2008.07.076
DO - 10.1016/j.brainres.2008.07.076
M3 - Article
C2 - 18694738
AN - SCOPUS:51449113042
VL - 1233
SP - 63
EP - 78
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -