Effects of Neurofilamentous Axonopathy-Producing Neurotoxicants on In Vitro Production of ATP by Brain Mitochondria

Details

• Personal Author:
  Fowler SR ; Sickles DW ; Testino AR
• Description:
  The site and mode of action of acrylamide (ACR), y-diketone hexacarbons and 3,3'-iminodipropionitrile (IDPN) in producing a neurofilamentous axonopathy are unknown. Whether the neuropathy is caused by reductions in axonal transport produced by energy depletion is under investigation. Reductions in the quantity of proteins fast transported following a single dose of ACR or neurotoxic y-diketones have been reported. The current study examines the in vitro effects of these toxicants upon ATP production by mitochondria. Isolated rat brain mitochondria incubated for 30 min at 37 degrees C with neurotoxic doses of ACR (0.7 mM) or 3,4-dimethyl-2,5-hexanedione (0.25 mM) retained similar capacities for synthesis of ATP from pyruvate and endogenous concentrations of ATP compared to controls. 2,5-Hexanedione (2,5-HD; 4 mM) and IDPN (0.1%) significantly reduced the rate of synthesis (-22.5% and -15%, respectively); but only 2,5-HD decreased the endogenous concentration of ATP (-21.6%) following a single 30 min exposure. Toxicant action on ATP production is limited to 2,5-HD; the lack of correlation between the toxicant-induced changes in axonal transport and mitochondrial ATP production demonstrate the necessity to evaluate other structures as the critical site of action in producing axonal transport changes. [Description provided by NIOSH]
• Subjects:
  Animals Nervous System Occupational Health Safety
• Keywords:
  3,3'-Iminodipropionitrile Acrylamide Animal Studies Author Keywords: Acrylamide Y-diketone Hexacarbon Brain Function Energy Metabolism Mitochondrial ATP Production Neurotoxic Effects Neurotoxicity Neurotoxins Neurotransmitters Peripheral Neuropathy Proteins

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• ISSN:
  0006-8993
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  25-31
• Volume:
  528
• Issue:
  1
• NIOSHTIC Number:
  nn:20058132
• Citation:
  Brain Res 1990 Sep; 528(1):25-31
• Contact Point Address:
  D.W. Sickles, Department of Anatomy, Medical College of Georgia, Augusta, GA 30912-2000, U.S.A.
• CAS Registry Number:
  3,3’-Iminodipropionitrile (CAS RN 111-94-4) ; Acrylamide (CAS RN 79-06-1)
• Federal Fiscal Year:
  1990
• Performing Organization:
  Medical College of Georgia, Augusta, Georgia
• Peer Reviewed:
  True
• Start Date:
  19840801
• Source Full Name:
  Brain Research
• End Date:
  19880929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:491a1154d57b90dd3cc26dcda715be9a05f243391bd61c2fc0f2a41f4d648f49370363cfc04a6c18b1b4bae3cb9c980c03a8c41e473e297391a1512670f9b929
• Download URL:
  https://stacks.cdc.gov/view/cdc/221274/cdc_221274_DS1.pdf
• File Type:
  [PDF - 732.04 KB ]