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N-hexane neurotoxicity: a mechanism involving pyrrole adduct formation in axonal cytoskeletal protein.

Authors
DeCaprio-AP
Source
Neurotoxicology 1987 Jan; 8(1):199-210
NIOSHTIC No.
00167062
Abstract
Literature on the neurotoxic effects of n-hexane (110543) was reviewed, and hypotheses for mechanisms linking pyrrole (109977) formation in axonal cytoskeletal protein with nerve degeneration in gamma-diketone neuropathy were presented. Aggregated neurofilament masses caused by a proposed increase in hydrophobic interactions were hypothesized to become lodged at areas of axonal constriction, blocking nutrient transport into the distal axon. Tertiary structure alterations accompanying pyrrole formation at certain critical lysine-epsilon-amine functions in the neurofilament subunit proteins were hypothesized to underlie the neuropathy. A third hypothesis, involving charge neutralization of neurofilament proteins, implicated the loss of positive charge following the pyrrolylation reaction as the critical molecular lesion. The author postulated that the carboxy terminal tail of the neurofilament was the critical target in gamma-diketone neuropathy. This region was postulated to be particularly vulnerable to pyrrolylation due to its unusually high lysine content. It was hypothesized that this pyrrolylation induced structural and physicochemical alterations in the carboxy terminus, leading to cytoskeletal disorganization with subsequent blockade of axonal nutrient flow and ultimate nerve degeneration. Evidence to support this hypothesis was presented. The authors conclude that it is currently unclear whether pyrrolylation is sufficient to induce gamma-diketone neuropathy, or if secondary pyrrole autoxidation is also necessary.
Keywords
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Neurotoxicity; Pyrroles; Hexanes; Organic-solvents; Pathogenesis; Toxicology; Nerve-damage
Contact
Biochem and Genetic Toxicology New York State Dept of Health Empire State Plaza Albany, N Y 12201
CODEN
NRTXDN
CAS No.
110-54-3; 109-97-7
Publication Date
19870101
Document Type
Journal Article
Funding Amount
133853
Funding Type
Grant
Fiscal Year
1987
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-01972
Issue of Publication
1
ISSN
0161-813X
Priority Area
Neurotoxic Disorders; Neurotoxic-effects
Source Name
Neurotoxicology
State
NY
Performing Organization
New York State Dept of Health, New York, New York
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