title: Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs.
abstract: OBJECTIVE
  With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs.
  
  
  METHODS
  Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular apoptosis.
  
  
  RESULTS
  No change in lung weight was detected over the course of the study; however, cerium accumulation in the lungs, gross histological changes, an increased Bax to Bcl-2 ratio, elevated cleaved caspase-3 protein levels, increased phosphorylation of p38 MAPK, and diminished phosphorylation of ERK-1/2-MAPK were detected after CeO2 instillation (p<0.05).
  
  
  CONCLUSIONS
  Taken together, these data suggest that high-dose respiratory exposure to CeO2 nanoparticles is associated with lung inflammation, the activation of signaling protein kinases, and cellular apoptosis, which may be indicative of a long-term localized inflammatory response.
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; School of Kinesiology, College of Health Professions, Marshall University, Huntington, WV, USA ; Biotechnology Department, West Virginia State University, Institute, WV, USA ; Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C. Edwards School of Medicine, Huntington, WV, USA.
authors.forename: Siva K
authors.initials: SK
authors.lastname: Nalabotu
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Nandini D P K
authors.initials: ND
authors.lastname: Manne
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C. Edwards School of Medicine, Huntington, WV, USA.
authors.forename: Madhukar B
authors.initials: MB
authors.lastname: Kolli
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Geeta
authors.initials: G
authors.lastname: Nandyala
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Arvapalli
authors.affiliation: Health Effects Laboratory Division, NIOSH, Morgantown, WV, USA.
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Ma
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; School of Kinesiology, College of Health Professions, Marshall University, Huntington, WV, USA ; Biotechnology Department, West Virginia State University, Institute, WV, USA ; Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C. Edwards School of Medicine, Huntington, WV, USA ; Health Effects Laboratory Division, NIOSH, Morgantown, WV, USA ; Department of Pharmaceutical Sciences, Marshall University School of Pharmacy, Huntington, WV, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002563:Cerium / Q000737:chemistry; D007249:Inflammation; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002563:Cerium; C030583:ceric oxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: Cerium oxide nanoparticles; Inflammation; Lung; Mitogen-activated protein kinases