Evidence for multiple mechanisms responsible for 2,5-hexanedione-induced neuropathy

Details

• Personal Author:
  Abou-Donia MB ; Lapadula DM ; Suwita E
• Description:
  The roles of protein crosslinking and phosphorylation in 2,5- hexanedione (110134) (25HD) induced neuropathy were studied in rats. Male Sprague-Dawley-rats were administered 0.1, 0.25, 0.50, or 1% 25HD in their drinking water for up to 70 days. They were observed for clinical signs of toxicity. Surviving animals were killed at the end of the study and the spinal cords were removed. The neurofilament proteins were isolated and examined by two dimensional polyacrylamide gel electrophoresis, histochemical techniques, and immunoblotting using antineurofilament protein antibodies to evaluate changes in neurofilament protein expression and crosslinking. The extent of phosphorylation was determined by a radioimmunoassay technique. 25HD at 1% caused hindlimb paralysis and 90% mortality. The 0.25 and 0.5% doses caused mild to severe ataxia. The 0.1% dose did not cause any overt signs of toxicity. 25HD at 0.25 to 1% caused significant decreases in staining for neurofilament proteins having molecular weights of 210, 160, and 70 kilodaltons (kDa). The 210kDa protein was affected the most. Significant protein crosslinking was induced by all 25HD doses. The extent of protein phosphorylation was significantly decreased in a dose dependent manner. All neurofilament proteins appeared to be shifted to an isoelectric point indicative of greater basicity. 25HD decreased the concentrations of low molecular weight immunoreactive proteins, indicating that neurofilament proteolysis was inhibited. The authors conclude that 25HD induced neuropathy appears to involve decreased neurofilament protein phosphorylation, decreased neurofilament proteolysis, and enhanced neurofilament crosslinking. Protein dephosphorylation probably occurs prior to crosslinking. [Description provided by NIOSH]
• Subjects:
  Butanones Drinking Water Immune System Laboratories Nervous System Occupational Health Safety
• Keywords:
  Author Keywords: 2,5-Hexanedione Drinking-water Immunochemistry In-vivo-studies Ketones Laboratory-animals Nerve-fibers Neurofilament Neuropathy Neurotoxic-effects NIOSH-Grant NIOSH-Publication Protein-chemistry Spinal-cord

  More +
• ISSN:
  0006-8993
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  123-131
• Volume:
  458
• Issue:
  1
• NIOSHTIC Number:
  nn:00213648
• Citation:
  Brain Res 1988 Aug; 458(1):123-131
• Contact Point Address:
  Pharmacology Duke University Department of Pharmacology Durham, N C 27710
• CAS Registry Number:
  2,5-Hexanedione (CAS RN 110-13-4)
• Federal Fiscal Year:
  1988
• NORA Priority Area:
  Neurotoxic Disorders ; Neurotoxic Effects
• Performing Organization:
  Duke University, Durham, North Carolina
• Peer Reviewed:
  True
• Start Date:
  19790401
• Source Full Name:
  Brain Research
• End Date:
  19980331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c1f5c7242db1afcbb49b136e85c86e1aca45ee9bb7155b9a9561dad4f1454d88924e1d71877d8a8a37619fbcd1943476e8c7c3eb4e1895a5721a27dc97c25cd1
• Download URL:
  https://stacks.cdc.gov/view/cdc/204710/cdc_204710_DS1.pdf
• File Type:
  [PDF - 293.35 KB ]