2,5-Hexanedione-Induced Changes in the Neurofilament Subunit Pools of Rat Peripheral Nerve

LoPachin, Richard M.; He, Deke; Reid, Maria L.

doi:10.1016/j.neuro.2004.09.007

Cited by 37 publications

(11 citation statements)

References 64 publications

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“…A profile of NFs decrements induced by HD has been repeatedly observed in spinal cord and sciatic nerve of rats, suggesting that HD intoxication is associated with the disruption of cytoskeleton turnover and maintenance, eventually results in axon atrophy [11,12]. Furthermore, our laboratory had also reported the alteration of NFs in cerebrum of rats during HD-induced neuropathy [13].…”

Section: Introductionmentioning

confidence: 73%

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Time-dependent Alteration of Cytoskeletal Proteins in Cerebral Cortex of Rat During 2,5-Hexanedione-induced Neuropathy

et al. 2007

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To investigate the mechanisms of the axonopathy induced by 2,5-hexanedione (2,5-HD), male Wistar rats were administered at a dosage of 400 mg/kg/day 2,5-HD (five times per week). The rats produced a slightly, moderately, or severely abnormal neurological changes, respectively, after 2, 4, or 8 weeks of treatment. The cerebrums were Triton-extracted and ultracentrifuged to yield a pellet fraction and a corresponding supernatant fraction. The relative levels of six cytoskeletal proteins (NF-L, NF-M, NF-H, alpha-tubulin, beta-tubulin, and beta-actin) in both fractions were determined by immunoblotting. The results showed that NFs content in HD-treated rats demonstrated a progressive decline as the intoxication of HD continued. As for microtubule proteins, the levels of alpha-tubulin and beta-tubulin demonstrated some inconsistent changes. The content of alpha-tubulin kept unchangeable, while the content of beta-tubulin increased significantly at the late stage of HD exposure. Furthermore, the content of beta-actin in both fractions remained unaffected throughout the study. These findings suggest that HD intoxication resulted in a progressive decline of NFs, which was highly correlated with the development of HD-induced neuropathy.

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Section: Introductionmentioning

confidence: 73%

“…Nerve homogenates were centrifuged at 100,000g for 1 h to yield a high-speed pellet (P) and a high-speed supernatant (S) [11,12,15,16]. Protein concentration of two fractions was determined by using BCA Protein assay Kit.…”

Section: Methodsmentioning

confidence: 99%

Time-dependent Alteration of Cytoskeletal Proteins in Cerebral Cortex of Rat During 2,5-Hexanedione-induced Neuropathy

et al. 2007

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“…Recently, many investigations have shown that cytoskeleton may be the primary target of some neurotoxicant. 2,5-Hexanedione, a neurotoxicant similar to CS 2 , could disrupt the turnover of major cytoskeletal elements, destroy the maintenance of axon, and finally cause the distal axonopathy [14][15][16]. Furthermore, a significant decrease of NFs content was observed in the cerebral cortex of rats treated with CS 2 in our recent studies [17].…”

Section: Introductionmentioning

confidence: 75%

“…Nerve homogenates were centrifuged at 100,000g for 1 h to yield a high-speed pellet (P) and a high-speed supernatant (S) [14,15,24,25]. Protein concentration of two fractions was determined by using BCA Protein Assay Kit.…”

Section: Animal Treatment and Neurological Testingmentioning

confidence: 99%

Carbon Disulfide-Induced Alterations of Neurofilaments and Calpains Content in Rat Spinal Cord

et al. 2006

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To investigate the mechanism of carbon disulfide-induced neuropathy, male Wistar rats were randomly divided into two experimental groups and one control group. The rats in two experimental groups were treated with carbon disulfide by gavage at dosages of 300 and 500 mg/kg/day, respectively, five times per week for 12 weeks. Spinal cords of carbon disulfide-intoxicated rats and their age-matched controls were Triton-extracted and ultracentrifuged to yield a pellet fraction of neurofilament (NF) polymer and a corresponding supernatant fraction. Then, the contents of NF triplet proteins (NF-H, NF-M, NF-L) and two calpain isoforms (m-calpain and mu-calpain) in both fractions were determined by immunoblotting. In the meantime, the mRNA levels of NF-H, NF-M, and NF-L in spinal cords were quantified using reverse transcriptase-polymerase chain reaction. Results showed that in the pellet fraction, the contents of three NF subunits in both treated groups decreased significantly except NF-L in low dose group. In the supernatant fraction, the pattern of NFs alteration varied according to dose-levels. Compared to controls, three neurofilmant subunits in the high dose group displayed significant reduction consistently. However, in the low dose group, they remained unaffected. As for calpains, the contents of mu-calpain in both fractions increased significantly regardless of carbon disulfide dose-levels. Meanwhile, m-calpain demonstrated a significant decline in the supernatant fraction, and remained unchangeable in the pellet fraction compared to the control group. Furthermore, the levels of mRNA expression of NF-H, NF-M, and NF-L genes were elevated consistently in CS(2)-treated groups. These findings suggested that carbon disulfide intoxication was associated with obvious alterations of NFs content in rat spinal cord, which might be involved in the development of carbon disulfide neurotoxicity.

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“…Among the nociceptive effects of HEX, peripheral neuropathy is the most severe and has been recognized as an occupational disease 3,4 . Neuropathy is caused by the main HEX metabolite, 2,5-hexanedione (2,5-HD), which binds to DNA, RNA and axon proteins [5][6][7] . The most widely used bioindicator in the monitoring of workers exposed to HEX is urinary 2,5-HD due to its high correlation with environmental exposure to HEX as reported by various investigators [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Urinary 2,5-hexanedione in workers exposed to n-hexane: influence of the sample treatment

Nolasco¹,

Gusmão²,

Siqueira³

2007

Quím. Nova

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Recebido em 24/2/06; aceito em 6/9/06; publicado na web em 26/3/07The aim of the present study was to determine 2,5-hexanedione (2,5-HD), a metabolite of n-hexane, by gas chromatography/flame ionization detection in 31 workers exposed to n-hexane after two types of sample pretreatment, i.e., with (total 2,5-HD) and without (free 2,5-HD) acid hydrolysis. The mean urinary 2,5-HD was 0.52 mg/L (free) and 2.88 mg/L (total), this difference being significant (Student t-test, p ≤ 0.05). The differences in the results according to the sample treatment support the need to modify the current Brazilian legislation, which proposes the analysis of 2,5-HD without indicating whether it is the free or total metabolite.

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2,5-Hexanedione-Induced Changes in the Neurofilament Subunit Pools of Rat Peripheral Nerve

Cited by 37 publications

References 64 publications

Time-dependent Alteration of Cytoskeletal Proteins in Cerebral Cortex of Rat During 2,5-Hexanedione-induced Neuropathy

Time-dependent Alteration of Cytoskeletal Proteins in Cerebral Cortex of Rat During 2,5-Hexanedione-induced Neuropathy

Carbon Disulfide-Induced Alterations of Neurofilaments and Calpains Content in Rat Spinal Cord

Urinary 2,5-hexanedione in workers exposed to n-hexane: influence of the sample treatment

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