Acrylamide administration alters protein phosphorylation and phospholipid metabolism in rat sciatic nerve

Journal Article · Tue May 01 04:00:00 EDT 1990 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(90)90323-M· OSTI ID:6721235

Berti-Mattera, L N; Eichberg, J; Schrama, L; LoPachin, R M ^[1]

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1. Univ. of Houston, Texas (USA)

The effects of ACR on protein phosphorylation and phospholipid metabolism were assessed in rat sciatic nerve. After 5 days of ACR administration (50 mg/kg/day) an increase in the incorporation of 32P into phosphatidylinositol-4,5-bisphosphate, phosphatidylinositol-4-phosphate, and phosphatidylcholine was detected in proximal sciatic nerve segments. In contrast, no changes in phospholipid metabolism were observed in distal segments. After 9 days of ACR treatment when neurotoxicological symptoms were clearly apparent, a generalized increase in radiolabel uptake into phospholipids was noted exclusively in proximal nerve regions. ACR-induced increases in phospholipid metabolism were toxicologically specific since comparable administration of MBA (108 mg/kg/day X 5 or 9 days) produced only minor changes. ACR intoxication was also associated with a rise in sciatic nerve protein phosphorylation. After 9 days of ACR treatment, phosphorylation of beta-tubulin, P0, and several unidentified proteins (38 and 180 kDa) was increased in distal segments. In contrast, chronic administration of MBA caused increases in phosphorylation of beta-tubulin and the major myelin proteins of proximal nerve segments. In cell free homogenates prepared from sciatic nerves of treated and control rats, MBA caused an increase in phosphorylation of major myelin proteins similar to its effect in intact proximal nerve segments. The most striking effect observed in nerve homogenates of ACR-treated rats was a marked decrease in phosphorylation of an 80-kDa protein. Addition of ACR (1 mM) to homogenates of normal nerve had no effect on protein phosphorylation. Our results indicate that changes in the phosphorylation of phospholipids and proteins in sciatic nerve might be a component of the neurotoxic mechanism of ACR.

• OSTI ID: 6721235
• Journal Information: Toxicology and Applied Pharmacology; (USA), Journal Name: Toxicology and Applied Pharmacology; (USA) Vol. 103:3; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACRYLAMIDE
AMIDES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
ESTERS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPIDS
MAMMALS
METABOLISM
NERVES
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHOLIPIDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
PROTEINS
RADIOISOTOPES
RATS
RODENTS
TOXICITY
TRACER TECHNIQUES
VERTEBRATES