Molecular speciation and dynamics of oxidized triacylglycerols in lipid droplets: mass spectrometry and coarse-grained simulations

Details

• Personal Author:
  Gabrilovich DI ; Kagan VE ; Klein-Seetharaman J ; Mohammadyani D ; O'Brien M ; Sadovsky Y ; Tyurin VA
• Description:
  Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands. Among the constituent LD neutral lipids, such as triacylglycerols, cholesterol esters, and free fatty acids, oxidizable polyunsaturated molecular species may be quite abundant, yet the structural and functional roles of their oxidation products have not been studied. Our previous work documented the presence of these peroxidized species in LDs. Assuming that hydrophilic oxygen-containing functionalities may markedly change the hydrophobic/hydrophilic molecular balance, here we utilized computational modeling to test the hypothesis that lipid peroxidation causes redistribution of lipids between the highly hydrophobic core and the polar surface (phospho)lipid monolayer-the area enriched with integrated enzymatic machinery. Using quantitative liquid chromatography/mass spectrometry, we characterized molecular speciation of oxTAGs in LDs of dendritic cells in cancer and hypoxic trophoblasts cells as two cellular models associated with dyslipidemia. Among the many types of oxidized lipids identified, we found that oxidatively truncated forms and hydroxyl derivatives of TAGs were the prevailing oxidized lipid species in LDs in both cell types. Using coarse-grained molecular dynamics (CG-MD) simulations we established that lipid oxidation changed their partitioning whereby oxidized lipids migrated into the outer monolayer of the LD, where they can affect essential metabolic pathways and undergo conversions, possibly leading to the formation of oxygenated lipid mediators. [Description provided by NIOSH]
• Subjects:
  Chemistry Energy Metabolism Lipids Lung Lung Diseases Neoplasms Occupational Health Pathology Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Author Keywords: Cancer Cancer Cell-function Cellular-function Chemical-analysis Chemical-composition Chemical-properties Chemical-reactions Hypoxia Lipid Droplet Lipid Oxidation Metabolism Neutral Lipids Oxidation Tumors

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• ISSN:
  0891-5849
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  53-60
• Volume:
  76
• NIOSHTIC Number:
  nn:20046681
• Citation:
  Free Radic Biol Med 2014 Nov; 76:53-60
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Free Radical Biology and Medicine
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8dad3d15d03a24e017ff00bfd25f5e05412db04e7396b2ac6b93a0002806b4e94f2dab928ef6b8b2da890dffb1ace4c82c132ca151fefb0ca38a9729930b6556
• Download URL:
  https://stacks.cdc.gov/view/cdc/202033/cdc_202033_DS1.pdf
• File Type:
  [PDF - 4.58 MB ]