Configuration of Thiols Dictates Their Ability to Promote Iron-Induced Reactive Oxygen Species Generation

Details

• Personal Author:
  Bondy SC ; Campbell A ; Yang EY
• Description:
  Iron catalyzes the production of reactive oxygen species (ROS) through the Fenton reaction. The modification of this phenomenon in the presence of various thiol compounds that are nominally reducing agents has been studied. Using the synaptosomal/mitochondrial (P2) fraction of rat cerebral cortex as a biological source of reactive oxygen species (ROS) production, we studied the influence of four compounds, glutathione (GSH), cysteine, N-acetyl-cysteine (NAC), and homocysteine on iron-induced ROS production. None of the thiol compounds alone, at the concentrations used, affected the basal rate of ROS production in the P2 fraction. GSH, homocysteine and NAC did not alter Fe-induced ROS generation, while cysteine greatly potentiated ROS formation. Measurement of the rate of ROS production in the presence of varying concentrations of cysteine together with 20 µM ferrous iron revealed a dose-response relationship. The mechanism whereby free cysteine, but not the cysteine-containing peptide GSH, homocysteine or NAC with a blocked amino group, exacerbates the prooxidant properties of ferrous iron probably involves formation of a complex between iron, a sulfhydryl and a free carboxyl residue located at a critical distance from the -SH group. Cysteine-iron interactions may, in part, account for the excessive toxicity of free cysteine in contrast to GSH and NAC. [Description provided by NIOSH]
• Subjects:
  Animals Ferrous Compounds Free Radicals Occupational Health Safety Sulfhydryl Compounds
• Keywords:
  Animal Studies Cellular Function Free Radical Generation Free Radicals Iron Reactive Oxygen Species ROS Thiols Toxic Effects
• ISSN:
  1351-0002
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  371-375
• Volume:
  5
• Issue:
  6
• NIOSHTIC Number:
  nn:20058222
• Citation:
  Redox Rep 2000 Dec; 5(6):371-375
• Contact Point Address:
  Dr Stephen C. Bondy, Center for Occupational and Environmental Health, Department of Community of Environmental Medicine, University of California, Irvine, CA. 92697- 1820, USA
• Email:
  scbondy@uci.edu
• CAS Registry Number:
  Glutathione (CAS RN 70-18-8) ; Iron (CAS RN 7439-89-6) ; L-(+)-Cysteine (CAS RN 52-90-4) ; N-Acetyl-L-cysteine (CAS RN 616-91-1)
• Federal Fiscal Year:
  2001
• Performing Organization:
  University of California, School of Public Health, Los Angeles, CA
• Peer Reviewed:
  True
• Start Date:
  19990701
• Source Full Name:
  Redox Report
• End Date:
  20040630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a09db7e7195abc3846244523d8df32469bc21b26a7379b9c969c308d324351007ea44e6445d4432de4aa16d245d9de4eec707ee80db5de4f1d36f91b728cbd1b
• Download URL:
  https://stacks.cdc.gov/view/cdc/221355/cdc_221355_DS1.pdf
• File Type:
  [PDF - 287.31 KB ]