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Acrylamide and carbon disulfide treatments increase the rate of rat brain tubulin polymerization

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Molecular and Chemical Neuropathology

Abstract

Acrylamide and carbon disulfide produce central-peripheral distal axonopathy in experimental animals and humans. The main feature of this disease is the focal swellings containing neurofilaments in distal axons, followed by nerve degeneration beyond these swellings. We studied the possible role of tubulin assembly kinetics in this disease. The rats were either administered acrylamide (50 mg/kg, ip, saline) or exposed to carbon disulfide (700 ppm, 9h) via inhalation for 12 and 15 d, respectively. Tubulin, purified from both acrylamide-(10.37±0.3 vs 11.3±0.15) and carbon disulfide-treated (9.72±0.5 vs 11.18±0.25) rat brains showed increase inV max (OD/min × 103) of its polymerization. However, only acrylamide treatment showed a decrease in time toV max, when brain supernatant was used for tubulin polymerization. In vitro addition of acrylamide (0.1–1 mM) to bovine brain tubulin also showed a decrease in time toV max (16–21%) of its polymerization. Carbon disulfide treatment of rats, on the other hand, showed a decrease in MAP-2 and an increase in a 120-kDa peptide concentration. The latter showed immunoreactivity with anti-MAP-2. The increase in the rate of tubulin polymerization by acrylamide and carbon disulfide treatment may alter the rate of transport of axonal consituents, including neurofilament, and contribute toward their accumulation in the focal swellings observed in this neuropathy.

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Abbreviations

DFP:

diisopropyl phosphorofluoridate

DTT:

dithiothreitol

DMHD:

3,4-dimethyl-2,5-hexanedione

EGTA:

ethyleneglycol-bis(β-aminoethyl ether),N, N, N′, N′-tetraacetic acid

EDTA:

ethylenediaminetetraacetic acid

GTP:

guanosine-5′-triphosphate

2,5-HD:

2,5-hexanedione

IDPN:

β, β′-imino-3-dipropionitrile

PMSF:

phenylmethylsulfonyl fluoride

PIPES:

piperazine-N,N′-bis[2-ethanesulfonic acid]

PAGE:

polyacrylamilde gel electrophoresis

SDS:

sodium dodecyl sulfate

TEMED:

N,N,N′,N′-tetramethylethylenediamine

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Authors and Affiliations

  1. Department of Pharmacology, Duke University Medical Center, 27708, Durham, NC

    Ram P. Gupta & Mohamed B. Abou-Donia

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  1. Ram P. Gupta
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  2. Mohamed B. Abou-Donia
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Gupta, R.P., Abou-Donia, M.B. Acrylamide and carbon disulfide treatments increase the rate of rat brain tubulin polymerization. Molecular and Chemical Neuropathology 30, 223–237 (1997). https://doi.org/10.1007/BF02815100

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  • DOI: https://doi.org/10.1007/BF02815100

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