title: Delivery of a protein transduction domain-mediated Prdx6 protein ameliorates oxidative stress-induced injury in human and mouse neuronal cells.
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.
authors.affiliation: Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska;
authors.forename: Shatrunjai P
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska;
authors.forename: Bhavana
authors.initials: B
authors.lastname: Chhunchha
authors.affiliation: Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska;
authors.forename: Nigar
authors.initials: N
authors.lastname: Fatma
authors.affiliation: Department of Ophthalmology, Kanazawa Medical University, Kanazawa, Japan; and.
authors.forename: Eri
authors.initials: E
authors.lastname: Kubo
authors.affiliation: Department of Neurology, Creighton University, Omaha, Nebraska.
authors.forename: Sanjay P
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska; dpsingh@unmc.edu.
authors.forename: Dhirendra P
authors.initials: DP
authors.lastname: Singh
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014162:Transfection
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse
keywords: NF-κB; Prdx6; hydrogen peroxide; reactive oxygen species; transduction domain