Covalent Binding of the Organophosphate Insecticide Profenofos to Tyrosine On Α- and Β-Tubulin Proteins

Details

• Personal Author:
  Baker MR ; Chu S ; Leong G ; Letcher RJ ; Li QX
• Description:
  Organophosphorus (OP) compounds can bind covalently to many types of proteins and form protein adducts. These protein adducts can indicate the exposure to and neurotoxicity of OPs. In the present work, we studied adduction of tubulin with the OP insecticide profenofos in vitro and optimized the method for detection of adducted peptides. Porcine tubulin was incubated with profenofos and was then digested with trypsin, followed by mass spectrometric identification of the profenofos-modified tubulin and binding sites. With solvent-assisted digestion (80% acetonitrile in digestion solution), the protein was digested for peptide identification, especially for some peptides with low mass. The MALDI-TOF-MS and LC-ESI-TOF-MS analysis results showed that profenofos bound covalently to Tyr83 in porcine a-tubulin (TGTY*83R) and to Tyr281 in porcine ß-tubulin (GSQQY*281R) with a mass increase of 166.02 Da from the original peptide fragments of porcine tubulin proteins. Tyrosine adduct sites were also confirmed by MALDI-TOF/TOF-MS analysis. This result may partially explain the neurotoxicity of profenofos at low doses and prolonged periods of exposure. [Description provided by NIOSH]
• Subjects:
  Insecticides Occupational Health Safety
• Keywords:
  Author Keywords: Adduct Exposure LC-Q-TOF-MS MALDI-TOF/TOF-MS Mass Spectrometry Organophosphate Organophosphorus Compounds Profenofos Protein Biochemistry Proteins Tubulin

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• ISSN:
  0045-6535
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  California ; Hawaii ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  154-159
• Volume:
  199
• NIOSHTIC Number:
  nn:20051853
• Citation:
  Chemosphere 2018 May; 199:154-159
• Contact Point Address:
  Qing X. Li, Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, 1955 East West Road, Honolulu, HI, 96822, USA
• Email:
  qingl@hawaii.edu
• CAS Registry Number:
  Profenofos (CAS RN 41198-08-7)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of California - Davis
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Chemosphere
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b17ab787d3ac90561655354df212c6fe67f9b33c888ec09bf9e716000aa1d8e582bbf001ee05af624037bad8a6e8ca1f163d20c5e8b9b600439cc00f95c03ca3
• Download URL:
  https://stacks.cdc.gov/view/cdc/211560/cdc_211560_DS1.pdf
• File Type:
  [PDF - 890.17 KB ]