Mitochondrial microRNA dysregulation contributes to acute cardiac dysfunction following pulmonary mountaintop mining particulate matter exposure

Details

• Personal Author:
  Erdely A ; Hollander JM ; Knuckles TL ; Nichols CE ; Nurkiewicz TR ; Shepherd DL ; Thapa D ; Zeidler-Erdely PC
• Description:
  Heart disease is the leading cause of mortality worldwide and is exacerbated in areas surrounding active mountaintop mining operations. Mountaintop mining generates particulate aerosols and thus creates unique air pollution. Mitochondrial dysfunction has been identified following exposure, yet the causative mechanisms are unidentified. MicroRNAs contribute to homeostatic and adaptive mechanisms and dysregulation contributes to the progression of heart disease. The goal of this study was to determine the effect of mountaintop mining particulate matter (PMMTM) on cardiac function and microRNA dysregulation. Adult male Sprague-Dawley rats and FVB mice were exposed to PMMTM collected from areas surrounding active mountaintop mining operations using intratracheal instillation and pharyngeal aspiration, respectively. Twenty-four hours post-exposure, cardiac functional measurements and mitochondrial isolations were performed. Cardiac dysfunction was indicated in both species compared to their sham control by decreased ejection fraction and fractional shortening. Following mitochondrial isolation, RNA was isolated and RT-qPCR was used to assess microRNA levels within the mitochondria. In both species, miR-378 was increased within the mitochondria following PMMTM exposure. Finally, we identified ATP synthase F0 subunit 6 (ATP6) as a potential target of miR-378 regulation. Immunoblotting identified a decrease in ATP6 protein content in the mitochondria of both species. In conclusion, this study provides evidence that PMMTM exposure increases mitochondrial microRNA content that contributes to mitochondrial dysfunction leading to cardiac dysfunction. [Description provided by NIOSH]
• Subjects:
  Aerosols Air Pollutants, Occupational Air Pollution, Indoor Cardiovascular Diseases Cardiovascular System Cells, Cultured Environmental Exposure Environmental Monitoring Environmental Pollution Enzymes Genetics Inhalation Exposure Laboratories Mining Occupational Health Particulate Matter Safety Toxicology

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• Keywords:
  Adenosines Aerosol-particles Air-contamination Airborne-particles Cardiac-function Cardiovascular-system-disorders Cell-alteration Cell-culture-techniques Cell-metabolism Environmental-pollution Enzyme-activity Exposure-assessment Gene-mutation Genes Heart Immunological-tests Inhalants Laboratory-animals Laboratory-testing Mining-industry Particulates Proteins Recombinant-DNA Surface-mining

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045986
• Citation:
  Toxicologist 2015 Mar; 144(1):343
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d7056d1b04ec7c2518588418a1b29c0f2498519c0941e87d63f30a278f30e25fd5ba8a084bf3973cbb08f0b13efab891c7ec0c135a11a64411749630448f1362
• Download URL:
  https://stacks.cdc.gov/view/cdc/201185/cdc_201185_DS1.pdf
• File Type:
  [PDF - 218.51 KB ]