title: Redox-Sensitive Cerium Oxide Nanoparticles Protect Human Keratinocytes from Oxidative Stress Induced by Glutathione Depletion.
abstract: Cerium oxide nanoparticles (CeNPs) have gathered much attention in the biomedical field due to its unique antioxidant property. It can protect cells and tissues from oxidative stress induced damage due to its autoregenerative redox cycle. Our study explores the antioxidant and antigenotoxic behavior of PEGylated CeNPs toward oxidative insult produced by buthionine sulfoximine (BSO) in human keratinocytes (HaCaT cells). BSO inhibits the γ-glutamylcysteinesynthetase (γ-GCS) enzyme and thus acts as a glutathione (GSH) depleting agent to modulate the cellular redox potential. GSH is a natural ROS scavenger present in the mammalian cells, and its depletion causes generation of reactive oxygen species (ROS). In this study, we challenged HaCaT cells (keratinocytes) with BSO to alter the redox potential within the cell and monitored toxicity, ROS generation, and nuclear fragmentation. We also followed changes in expressions of related proteins and genes. We found that PEGylated CeNPs can protect HaCaT cells from BSO-induced oxidative damage. BSO-exposed cells, preincubated with PEGylated CeNPs, showed better cell survival and significant decrease in the intracellular levels of ROS. We also observed decrease in lactate dehydrogenase (LDH) release and nuclear fragmentation in CeNP-treated cells that were challenged with BSO as compared to treatment with BSO alone. Exposure of HaCaT cells with BSO leads to altered expression of antioxidant genes and proteins, i.e., thioredoxin reductase (TrxR) and peroxiredoxin 6 (Prx6) whereas, in our study, pretreatment of PEGylated CeNPs reduces the need for induction of genes that produce enzymes involved in the defense against oxidative stress. Since, growing evidence argued the involvement of ROS in mediating death of mammalian cells in several ailments, our finding reinforces the use of PEGylated CeNPs as a potent pharmacological agent under the lower cellular GSH/GSSG ratios for the treatment of diseases mediated by free radicals.
authors: Division of Biological and Life Sciences, School of Arts and Sciences and ‡School of Engineering and Applied Sciences, Ahmedabad University , Navrangpura, Ahmedabad-380009, Gujarat, India.|Department of Molecular Biology and Microbiology, Burnett School of Biomedical Science and ∥Advanced Materials Processing and Analysis Centre, Nanoscience Technology Centre (NSTC), Materials Science and Engineering and College of Medicine, University of Central Florida , Orlando, Florida 32816, United States.
authors: Ragini
authors: R
authors: Singh
authors: Division of Biological and Life Sciences, School of Arts and Sciences and ‡School of Engineering and Applied Sciences, Ahmedabad University , Navrangpura, Ahmedabad-380009, Gujarat, India.|Department of Molecular Biology and Microbiology, Burnett School of Biomedical Science and ∥Advanced Materials Processing and Analysis Centre, Nanoscience Technology Centre (NSTC), Materials Science and Engineering and College of Medicine, University of Central Florida , Orlando, Florida 32816, United States.
authors: Ajay S
authors: AS
authors: Karakoti
authors: Division of Biological and Life Sciences, School of Arts and Sciences and ‡School of Engineering and Applied Sciences, Ahmedabad University , Navrangpura, Ahmedabad-380009, Gujarat, India.|Department of Molecular Biology and Microbiology, Burnett School of Biomedical Science and ∥Advanced Materials Processing and Analysis Centre, Nanoscience Technology Centre (NSTC), Materials Science and Engineering and College of Medicine, University of Central Florida , Orlando, Florida 32816, United States.
authors: William
authors: W
authors: Self
authors: Division of Biological and Life Sciences, School of Arts and Sciences and ‡School of Engineering and Applied Sciences, Ahmedabad University , Navrangpura, Ahmedabad-380009, Gujarat, India.|Department of Molecular Biology and Microbiology, Burnett School of Biomedical Science and ∥Advanced Materials Processing and Analysis Centre, Nanoscience Technology Centre (NSTC), Materials Science and Engineering and College of Medicine, University of Central Florida , Orlando, Florida 32816, United States.
authors: Sudipta
authors: S
authors: Seal
authors: Division of Biological and Life Sciences, School of Arts and Sciences and ‡School of Engineering and Applied Sciences, Ahmedabad University , Navrangpura, Ahmedabad-380009, Gujarat, India.|Department of Molecular Biology and Microbiology, Burnett School of Biomedical Science and ∥Advanced Materials Processing and Analysis Centre, Nanoscience Technology Centre (NSTC), Materials Science and Engineering and College of Medicine, University of Central Florida , Orlando, Florida 32816, United States.
authors: Sanjay
authors: S
authors: Singh
mesh_terms: D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002478:Cells, Cultured; D002563:Cerium / Q000737:chemistry*; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors*; D005978:Glutathione; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D053758:Nanoparticles; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D017382:Reactive Oxygen Species; D002563:Cerium; D019328:Buthionine Sulfoximine; C030583:ceric oxide; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione