Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage

Rajkumar Tulsawani, Lorena S. Kelly, Nigar Fatma, Bhavanaben Chhunchha, Eri Kubo, Anil Kumar, Dhirendra P. Singh

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Background: The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS)-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC) death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6) plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis.Results: We have shown that RGCs exposed to hypoxia (1%) or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM), revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6.Conclusion: Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.

Original languageEnglish (US)
Article number125
JournalBMC Neuroscience
Volume11
DOIs
StatePublished - Oct 5 2010

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Peroxiredoxin VI
Retinal Ganglion Cells
Neuroprotective Agents
Reactive Oxygen Species
Cell Death
Hypoxia
Proteins
Glaucoma
Transcriptional Activation
Real-Time Polymerase Chain Reaction
Cell Survival

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage. / Tulsawani, Rajkumar; Kelly, Lorena S.; Fatma, Nigar; Chhunchha, Bhavanaben; Kubo, Eri; Kumar, Anil; Singh, Dhirendra P.

In: BMC Neuroscience, Vol. 11, 125, 05.10.2010.

Research output: Contribution to journalArticle

Tulsawani, Rajkumar ; Kelly, Lorena S. ; Fatma, Nigar ; Chhunchha, Bhavanaben ; Kubo, Eri ; Kumar, Anil ; Singh, Dhirendra P. / Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage. In: BMC Neuroscience. 2010 ; Vol. 11.
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abstract = "Background: The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS)-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC) death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6) plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis.Results: We have shown that RGCs exposed to hypoxia (1{\%}) or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1{\%} oxygen or cobalt chloride (0-400 μM), revealed ~30{\%}-70{\%} apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6.Conclusion: Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.",
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