Temporal evaluation of multicompartment molecular signaling following an inhalation exposure to metal-rich particulate matter

Details

• Personal Author:
  Antonini JM ; Chen BT ; Erdely A ; Eye T ; Frazer DG ; Hollander JM ; Kashon ML ; Li S ; Liston A ; Nichols CE ; Salmen R ; Shah S ; Simeonova PP ; Stone S ; Tugendreich S ; Zeidler-Erdely PC
• Description:
  Adverse cardiovascular effects after particulate inhalation exposures have been reported; however, the mechanisms involved are largely unknown. For mechanistic insight, we investigated global transcriptional alterations in the target organ (lung) as well as several extrapulmonary tissues (heart, aorta, whole blood cells) following inhalation (40 mg/m3 for 3 h/d for 5 d a week for 10 d) to stainless steel welding fume. Tissues were collected 4 h and 28 d post-exposure, RNA was isolated and microarray results were analyzed using Ingenuity Pathway Analysis for pertinent biological and molecular networks associated with effects. Utilizing the upstream regulator (i.e. transcription factors, cytokines, growth factors) analysis, the lung had 285, blood cells 30, aorta 39, and heart 32 significantly altered mediators 4 h post-exposure. There was a graded decline in the total mediators at 28 d with the lung decreasing by 3%, blood cells 37%, aorta 77% and heart 100%. When examining the connectivity of signaling at 4 h, 90% of the upstream regulators in the blood cells were reflective of the lung response, 90% in the aorta, and 44% in the heart. Specific mediators of interest in the aorta (Mt2, Sele, Hspa1b, Vcam1) predictive of adverse vascular effects were increased. Mitochondrial dysfunction was the top canonical pathway in the heart with the top three signaling networks centering on altered energy metabolism. PPARGC1A, a transcription factor regulating mitochondrial biogenesis and function and induced by oxidative stress, was increased and linked to many of the altered cardiac upstream regulators and genes associated with mitochondrial dysfunction. In conclusion, systemic signaling, suggestive of oxidative stress-mediated cardiovascular dysfunction, was strongly reflective of the ongoing pulmonary response although the altered signaling was not sustained compared to the lung. [Description provided by NIOSH]
• Subjects:
  Blood Cardiovascular Diseases Cardiovascular System Cells, Cultured Environmental Monitoring Genetics Growth Inhalation Exposure Lung Metals Occupational Health Particulate Matter Respiratory System Safety Toxicology Welding

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• Keywords:
  Blood-cells Cardiovascular-system-disorders Cell-alteration Cell-culture-techniques Cell-metabolism Exposure-assessment Genes Growth-factors Heart Inhalants Metal-fumes Molecular-structure Organs Oxidative-processes Particulates Pulmonary-system Recombinant-DNA Signaling-systems Stainless-steel Tissue-culture

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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:20045984
• Citation:
  Toxicologist 2015 Mar; 144(1):341
• CAS Registry Number:
  Stainless Steel (CAS RN 12597-68-1)
• Federal Fiscal Year:
  2015
• 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-512:2a3f89a57626c717cef3f3f441088f5404c2fd650f29c24d7e5974785c87facf0cc359bb97bdd8be30eb224f90d7cb529dbf25c6d53113a67a92cf8a929c9bc5
• Download URL:
  https://stacks.cdc.gov/view/cdc/201183/cdc_201183_DS1.pdf
• File Type:
  [PDF - 211.35 KB ]