Dust from hog confinement facilities impairs Ca2+ mobilization from sarco(endo)plasmic reticulum by inhibiting ryanodine receptors

Details

• Personal Author:
  Bidasee KR ; Dodmane P ; Moore CJ ; Romberger DJ ; Shao CH ; Tian C ; Toews ML
• Description:
  Individuals working in commercial hog confinement facilities have elevated incidences of headaches, depression, nausea, skeletal muscle weakness, fatigue, gastrointestinal disorders, and cardiovascular diseases, and the molecular mechanisms for these nonrespiratory ailments remain incompletely undefined. A common element underlying these diverse pathophysiologies is perturbation of intracellular Ca(2+) homeostasis. This study assessed whether the dust generated inside hog confinement facilities contains compounds that alter Ca(2+) mobilization via ryanodine receptors (RyRs), key intracellular channels responsible for mobilizing Ca(2+) from internal stores to elicit an array of physiologic functions. Hog barn dust (HBD) was extracted with phosphate-buffered saline, sterile-filtered (0.22 µm), and size-separated using Sephadex G-100 resin. Fractions (F) 1 through 9 (Mw >10,000 Da) had no measurable effects on RyR isoforms. However, F10 through F17, which contained compounds of Mw =2,000 Da, modulated the [(3)H]ryanodine binding to RyR1, RyR2, and RyR3 in a biphasic (Gaussian) manner. The Ki values for F13, the most potent fraction, were 3.8 +/- 0.2 µg/ml for RyR1, 0.2 +/- 0.01 µg/ml and 19.1 +/- 2.8 µg/ml for RyR2 (two binding sites), and 44.9 +/- 2.8 µg/ml and 501.6 +/- 9.2 µg/ml for RyR3 (two binding sites). In lipid bilayer assays, F13 dose-dependently decreased the open probabilities of RyR1, RyR2, and RyR3. Pretreating differentiated mouse skeletal myotubes (C2C12 cells) with F13 blunted the amplitudes of ryanodine- and K(+)-induced Ca(2+) transients. Because RyRs are present in many cell types, impairment in Ca(2+) mobilization from internal stores via these channels is a possible mechanism by which HBD may trigger these seemingly unrelated pathophysiologies. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Air Pollution, Indoor Animals Calcium Compounds Dust Energy Metabolism Laboratories Men Musculoskeletal System Occupational Health Particulate Matter Risk Assessment Risk Factors Safety Women

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• Keywords:
  Air-contamination Airborne-dusts Airborne-particles Calcium-compounds Dust-exposure Dusts Exposure-levels Humans Laboratory-animals Metabolism Muscles Pollutants Pollution Risk-factors

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• ISSN:
  8750-7587
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  114
• Issue:
  5
• NIOSHTIC Number:
  nn:20043634
• Citation:
  J Appl Physiol 2013 Mar; 114(5):665-674
• Contact Point Address:
  Keshore R. Bidasee, 985800 Nebraska Medical Center, Durham Research Center, DRC 3047, Omaha, NE 68198-5800
• Email:
  kbidasee@unmc.edu
• CAS Registry Number:
  Calcium (CAS RN 7440-70-2) ; Potassium (CAS RN 7440-09-7)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  True
• Start Date:
  20060801
• Source Full Name:
  Journal of Applied Physiology
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:91d4d4bd2f46b651ba162182d3b647cf9dc619896a3a077712f64b539d093c511ad234da651f5170c3b100e6d956f501a71d76ee2d80106191dc0fdaaa72fe2e
• Download URL:
  https://stacks.cdc.gov/view/cdc/195479/cdc_195479_DS1.pdf
• File Type:
  [PDF - 1.74 MB ]