advertisement
Abstract #27545 Published in IGR 12-4
Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage
Tulsawani R; Kelly LS; Fatma N; Chhunchha B; Kubo E; Kumar A; Singh DPBMC Neuroscience 2010; 11: 125
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-(kappa)B. 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 (mu)M), 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-(kappa)B 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. (copyright) 2010 Tulsawani et al; licensee BioMed Central Ltd.
D.P. Singh. Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE, 68 198, United States. dpsingh@unmc.edu
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.8 Pharmacology (Part of: 3 Laboratory methods)
