Hexanedione effects on protein phosphorylation in rat peripheral nerve

Horan, Kelly L.; Eichberg, Joseph; Berti‐Mattera, Liliana N.; LoPachin, Richard M.

doi:10.1016/0006-8993(89)90072-3

Cited by 14 publications

(3 citation statements)

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“…However, the diametrically opposed alterations in elemental composition that distinguish 2,5-HD swellings from those produced by acrylamide suggest that the respective mechanisms are different. Finally, evidence from this laboratory (Horan et al, 1989) and others (Lapadula et al, 1988;Watson et al, 1991) indicate that specific alterations in nervous tissue protein phosphorylation are a component ofhexanedione axonopathy. Thus, the mechanism ofhexacarbon neuropathy might be complex and involve effects on multiple axonal systems (Lapadula et al, 1988) .…”

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confidence: 65%

“…; acetonyIacetone, 97% pure) according to two treatment paradigms: i.p . injection using a dose of 400 mg/kg/day in 0.9% NaCl (saline; Horan et al ., 1989), or oral ingestion using an exposure level of 0.4% (wt/vol) in drinking water. The 0.4% oral dose represents the highest concentration of 2,5-HD tolerated (indicated by food and water intake) by rats used in this study.…”

Section: Animals and Treatmentsmentioning

confidence: 99%

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2,5‐Hexanedione Alters Elemental Composition and Water Content of Rat Peripheral Nerve Myelinated Axons

LoPachin

Lehning

Stack

et al. 1994

Journal of Neurochemistry

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Effects of 2,5-hexanedione on elemental concentrations and water content of peripheral nerve myelinated axons were determined using electron probe x-ray microanalysis. Axons (small, medium, and large) were analyzed in unfixed cryosections from rat tibial and proximal sciatic nerve samples. Animals were intoxicated with 2,5-hexanedione by two dosing paradigms: intraperitoneal or oral . Regardless of the route of exposure, internodal axoplasm of small and medium axons from both nerve regions exhibited selective, progressive reductions in dry weight K concentrations and water content. When calculated on a wet weight basis, K levels were comparable to or slightly above control values in tibial nerve, whereas in sciatic nerve, small transient decreases in wet weight K were evident. These changes in K and water correlated with the development of axonal atrophy. The wet and dry weight internodal elemental changes reported here do not suggest a metabolic or axolemmal defect, but rather imply a homeostatic response possibly related to the process of axonal atrophy. Giant axonal swellings were primarily associated with oral 2,5-hexanedione intoxication, and corresponding analyses revealed few changes in element or water content compared with control . The absence of significant alterations in these swellings is consistent with mechanical expansion of the axon probably as a function of accumulating neurofilaments. Key Words: 2,5-Hexanedione-Electron probe x-ray microanalysis-Distal axonopathy-Chemical neurotoxicant-Myelinated axon .

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mentioning

confidence: 65%

Section: Animals and Treatmentsmentioning

confidence: 99%

2,5‐Hexanedione Alters Elemental Composition and Water Content of Rat Peripheral Nerve Myelinated Axons

LoPachin

Lehning

Stack

et al. 1994

Journal of Neurochemistry

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“…Neutral proteinase activities are suggested to play an important role in the turnover of proteins in neuronal perikaryon and axon, and digestion of the transported cytoskeletal proteins in synaptic terminals (31,32). Earlier studies have demonstrated reduced NF phosphorylation in HD treated rats (14,33). Dephosphorylation of NF proteins enhances their susceptibility to degradation by calpain (34).…”

Section: Discussionmentioning

confidence: 99%

2,5-Hexanedione Induced Decrease in Cytoskeletal Proteins of Rat Sciatic?tibial Nerve

et al. 2005

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Exposure chronically to n-hexane produces peripheral-central axonopathy mediated by 2,5-hexanedione (HD). Previous studies have demonstrated decreases in neurofilament (NF) contents of peripheral and central nervous regions from rats intoxicated with HD, and recent analysis has demonstrated that axonal atrophy, instead of NF-filled swellings, is a specific component of morphologic alterations. To deeply investigate the alterations of cytoskeletal proteins in HD peripheral neuropathy, the relative levels of NF-L, NF-M, NF-H, alpha-tubulin, beta-tubulin and beta-actin of rat sciatic-tibial nerves were determined by SDS-PAGE and immunoblotting. HD was administrated to Wistar rats by intraperitoneal injection at dosage of 200 or 400 mg/kg/day (five-times per week). Rats were sacrificed after 6 weeks of treatment, and sciatic-tibial nerves were dissected, homogenized, and used for the determination of cytoskeletal proteins. Except for supernatant NF-L that could not be assayed, the results showed HD intoxication was associated with significant decreases in NF subunits in both of the supernatant and the pellet fractions of sciatic-tibial nerve homogenates (P < 0.01), and obvious reductions in alpha-tubulin, beta-tubulin and beta-actin only in the supernatant (P < 0.05 or P < 0.01). Among these alterations, the falls in the levels of NF subunits tended to be greater compared to those of the other cytoskeletal proteins in all HD-exposed groups, and the trend for decrements in NF-M was greater than those in the other NF subunits. Thus, HD intoxication was associated with significant declines in cytoskeletal protein contents in rat sciatic-tibial nerves, and the decreases might be related to the involvement of the peripheral axonopathy induced by HD.

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Comparative Study of Modification and Degradation of Neurofilament Proteins in Rats Subchronically Treated with Allyl Chloride, Acrylamide, or 2,5-Hexanedione

Nagano

Yamamoto

Harada

et al. 1993

Environmental Research

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Hexanedione effects on protein phosphorylation in rat peripheral nerve

Cited by 14 publications

References 15 publications

2,5‐Hexanedione Alters Elemental Composition and Water Content of Rat Peripheral Nerve Myelinated Axons

2,5‐Hexanedione Alters Elemental Composition and Water Content of Rat Peripheral Nerve Myelinated Axons

2,5-Hexanedione Induced Decrease in Cytoskeletal Proteins of Rat Sciatic?tibial Nerve

Comparative Study of Modification and Degradation of Neurofilament Proteins in Rats Subchronically Treated with Allyl Chloride, Acrylamide, or 2,5-Hexanedione

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