miRNA-378a as a Key Regulator of Cardiovascular Health Following Engineered Nanomaterial Inhalation Exposure

Details

• Personal Author:
  Abukabda AB ; Brandebura AN ; Durr AJ ; Fink GK ; Friend SA ; Goldsmith WT ; Hathaway QA ; Hollander JM ; Kunovac A ; Nichols CE ; Nurkiewicz TR ; Pinti MV ; Shepherd DL
• Description:
  Nano-titanium dioxide (nano-TiO2), though one of the most utilized and produced engineered nanomaterials (ENMs), diminishes cardiovascular function through dysregulation of metabolism and mitochondrial bioenergetics following inhalation exposure. The molecular mechanisms governing this cardiac dysfunction remain largely unknown. The purpose of this study was to elucidate molecular mediators that connect nano-TiO2 exposure with impaired cardiac function. Specifically, we were interested in the role of microRNA (miRNA) expression in the resulting dysfunction. Not only are miRNA global regulators of gene expression, but also miRNA-based therapeutics provide a realistic treatment modality. Wild type and MiRNA-378a knockout mice were exposed to nano-TiO2 with an aerodynamic diameter of 182 +/- 1.70 nm and a mass concentration of 11.09 mg/m3 for 4 h. Cardiac function, utilizing the Vevo 2100 Imaging System, electron transport chain complex activities, and mitochondrial respiration assessed cardiac and mitochondrial function. Immunoblotting and qPCR examined molecular targets of miRNA-378a. MiRNA-378a-3p expression was increased 48 h post inhalation exposure to nano-TiO2. Knockout of miRNA-378a preserved cardiac function following exposure as revealed by preserved E/A ratio and E/SR ratio. In knockout animals, complex I, III, and IV activities (approximately 2- to 6-fold) and fatty acid respiration (approximately 5-fold) were significantly increased. MiRNA-378a regulated proteins involved in mitochondrial fusion, transcription, and fatty acid metabolism. MiRNA-378a-3p acts as a negative regulator of mitochondrial metabolic and biogenesis pathways. MiRNA-378a knockout animals provide a protective effect against nano-TiO2 inhalation exposure by altering mitochondrial structure and function. This is the first study to manipulate a miRNA to attenuate the effects of ENM exposure. [Description provided by NIOSH]
• Subjects:
  Animals Cardiovascular System Energy Metabolism Environmental Exposure Laboratories Occupational Health Safety Titanium
• Keywords:
  Author Keywords: Cardiovascular Bioenergetics Cardiac Function Cardiovascular Health Exposure Levels Gene Expression Inhalation Exposure Laboratory Animals Metabolism Mitochondria Molecular Biology Nanomaterials Nanotechnology Proteins Titanium Dioxide

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• ISSN:
  1743-5390
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  398-406
• Volume:
  76
• Issue:
  6
• NIOSHTIC Number:
  nn:20054699
• Citation:
  Nanotoxicology 2019 Jun; 76(6):398-406
• Contact Point Address:
  John M. Hollander, Division of Exercise Physiology, West Virginia University School of Medicine, PO Box 9227, 1 Medical Center Drive, Morgantown, WV 26506
• Email:
  jhollander@hsc.wvu.edu
• CAS Registry Number:
  Titania (CAS RN 13463-67-7)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Nanotoxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b323efc4f7d898cdb5149be52b7b02a07240f209bf4f6c5cb3acb30701e4d9059c55a712ef99392397861b86f66eb0fb07f8772b5d8d4e4056648c57a9bf1bd8
• Download URL:
  https://stacks.cdc.gov/view/cdc/217149/cdc_217149_DS1.pdf
• File Type:
  [PDF - 2.34 MB ]