Peroxiredoxin 6 delivery attenuates TNF-α-and glutamate-induced retinal ganglion cell death by limiting ROS levels and maintaining Ca2+ homeostasis

Nigar Fatma, E. Kubo, M. Sen, N. Agarwal, Wallace B Thoreson, C. B. Camras, Dhirendra P Singh

Research output: Contribution to journalArticle

60 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)63-78
Number of pages16
JournalBrain Research
Volume1233
DOIs
StatePublished - Oct 3 2008

Fingerprint

Peroxiredoxin VI
Retinal Ganglion Cells
Glutamic Acid
Reactive Oxygen Species
Homeostasis
Cell Death
Glaucoma
Cellular Microenvironment
Nervous System Diseases
Retina
Real-Time Polymerase Chain Reaction
Apoptosis
Staining and Labeling
Messenger RNA

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 journalArticle

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