Delivery of a protein transduction domain-mediated Prdx6 protein ameliorates oxidative stress-induced injury in human and mouse neuronal cells

Shatrunjai P. Singh, Bhavana Chhunchha, Nigar Fatma, Eri Kubo, Sanjay Singh, Dhirendra P. Singh

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Oxidative stress or reduced expression of naturally occurring antioxidants during aging has been identified as a major culprit in neuronal cell/tissue degeneration. Peroxiredoxin (Prdx) 6, a protective protein with GSH peroxidase and acidic calcium-independent phospholipase A2 activities, acts as a rheostat in regulating cellular physiology by clearing reactive oxygen species (ROS) and thereby optimizing gene regulation. We found that under stress, the neuronal cells displayed reduced expression of Prdx6 protein and mRNA with increased levels of ROS, and the cells subsequently underwent apoptosis. Using Prdx6 fused to TAT transduction domain, we showed evidence that Prdx6 was internalized in human brain cortical neuronal cells, HCN-2, and mouse hippocampal cells, HT22. The cells transduced with Prdx6 conferred resistance against the oxidative stress inducers paraquat, H2O2, and glutamate. Furthermore, Prdx6 delivery ameliorated damage to neuronal cells by optimizing ROS levels and overstimulation of NF-κB. Intriguingly, transduction of Prdx6 increased the expression of endogenous Prdx6, suggesting that protection against oxidative stress was mediated by both extrinsic and intrinsic Prdx6. The results demonstrate that Prdx6 expression is critical to protecting oxidative stress-evoked neuronal cell death. We propose that local or systemic application of Prdx6 can be an effective means of delaying/postponing neuronal degeneration.

Original languageEnglish
Pages (from-to)C1-C16
JournalAmerican Journal of Physiology - Cell Physiology
Volume310
Issue number1
DOIs
StatePublished - Jan 1 2016

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Oxidative Stress
Wounds and Injuries
Proteins
Reactive Oxygen Species
Peroxiredoxin VI
Calcium-Independent Phospholipase A2
Paraquat
Protein Domains
Peroxidase
Glutamic Acid
Cell Death
Antioxidants
Apoptosis
Messenger RNA
Brain
Genes

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Physiology

Cite this

Delivery of a protein transduction domain-mediated Prdx6 protein ameliorates oxidative stress-induced injury in human and mouse neuronal cells. / Singh, Shatrunjai P.; Chhunchha, Bhavana; Fatma, Nigar; Kubo, Eri; Singh, Sanjay; Singh, Dhirendra P.

In: American Journal of Physiology - Cell Physiology, Vol. 310, No. 1, 01.01.2016, p. C1-C16.

Research output: Contribution to journalArticle

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