Preferential distribution of α-hexachlorocyclohexane into cerebral white matter

Portig, J.; Stein, Keith L.; Vohland, H. W.

doi:10.3109/00498258909034684

Cited by 16 publications

(3 citation statements)

References 14 publications

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“…A large number of pesticides result in tremor. The organochlorine pesticides (OCPs) are especially tremorogenic, and several specific OCPs (p,p′‐DDT, DDE, chlordane, chlordecone, and hexachlorocyclohexane) produce severe tremor either in exposed animals (rats, guinea pigs, bats, chicks, quails) or in humans 58–68…”

Section: Nature Vs Nurturementioning

confidence: 99%

A Stable Chemical SUMO1–Ubc9 Conjugate Specifically Binds as a Thioester Mimic to the RanBP2–E3 Ligase Complex

et al. 2015

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Ubiquitin and ubiquitin-like (Ubl) modifiers such as SUMO are conjugated to substrate proteins by E1, E2, and E3 enzymes. In the presence of an E3 ligase, the E2∼Ubl thioester intermediate becomes highly activated and is prone to chemical decomposition, thus making biochemical and structural studies difficult. Here we explored a stable chemical conjugate of the E2 enzyme from the SUMO pathway, Ubc9, with its modifier SUMO1 as a structural analogue of the Ubc9∼SUMO1 thioester intermediate, by introducing a triazole linkage by biorthogonal click chemistry. The chemical conjugate proved stable against proteolytic cleavage, in contrast to a Ubc9-SUMO1 isopeptide analogue obtained by auto-SUMOylation. Triazole-linked Ubc9-SUMO1 bound specifically to the preassembled E3 ligase complex RanBP2/RanGAP1*SUMO1/Ubc9, thus suggesting that it is a suitable thioester mimic. We anticipate interesting prospects for its use as a research tool to study protein complexes involving E2 and E3 enzymes.

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Section: Nature Vs Nurturementioning

confidence: 99%

A Stable Chemical SUMO1–Ubc9 Conjugate Specifically Binds as a Thioester Mimic to the RanBP2–E3 Ligase Complex

et al. 2015

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“…For instance, high concentrations of R-HCH in marine mammal brains indicate that this compound can cross the blood/brain barrier. R-HCH accumulation in rat brain white matter has also been documented; however, no functional consequences of this accumulation were detected in rats (85). More research is necessary to determine if organspecific accumulation of HCH isomers occurs in humans and whether any tissue specific toxic effects result.…”

Section: Animal Hch Residue Concentrationsmentioning

confidence: 99%

Differential Toxicity and Environmental Fates of Hexachlorocyclohexane Isomers

Willett

Ulrich

Hites

1998

Environ. Sci. Technol.

815

451

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The differential environmental fates and toxicities of the various hexachlorocyclohexane (HCH) isomers including lindane and isomers in the technical mixture will be the focus of this review. HCHs are one of the most widely used and most readily detected organochlorine pesticides in environmental samples. The relatively high volatility of HCH has led to global transport, even into formerly pristine locations such as the Arctic. Certain HCHs cause central nervous system, reproductive, and endocrine damage. Because γ-HCH is rapidly metabolized, the β-HCH isomer is consistently found in higher concentrations in human fat, blood, and breast milk. In contrast, Rand γ-HCH are the most prevalent isomers in soil, water, and air samples. The ratio of the Rto γ-isomers can be used to track global transport of HCHs. A new area of HCH research focuses on the selective degradation of the two R-HCH enantiomers in various environmental matrices. These HCH issues and recommendations for future HCH research are presented in this review.

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“…On the other hand, the α-isomer is not nearly as toxic to insects, but it accounts for 60−70% of the mixture. The main toxic action of HCH is central nervous system damage, and several studies have shown that these compounds accumulate in the brain of mammals where this toxic action occurs ( 3 , − .…”

Section: Introductionmentioning

confidence: 99%

Understanding Enantioselective Processes: A Laboratory Rat Model for α-Hexachlorocyclohexane Accumulation

Ulrich

Willett

Caperell-Grant

et al. 2001

Environ. Sci. Technol.

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Since cyclodextrin gas chromatography columns became popular for chiral separations, many researchers have noticed high enantiomeric ratios [ER: (+)-enantiomer/(-)-enantiomer] for alpha-HCH in the brains of wildlife. This investigation used the laboratory rat as a model for these phenomena. Rats were either pretreated with phenobarbital (PB) or left untreated and then dosed with alpha-HCH. Animals were sacrificed after 1 or 24 h. The ER averaged 0.95 +/- 0.01 in blood, 1.29 +/- 0.02 in fat, and 0.77 +/- 0.004 in liver. ERs in brain ranged from 2.8 +/- 0.5 to 13.5 +/- 0.4. Both the tissue concentration distribution and the ERs agree well with those previously reported in wildlife. To determine whether high brain ERs were due to enantioselective metabolism or transport through the blood-brain barrier, alpha-HCH exposed brain and liver tissue slices were compared. Concentrations in the brain slices did not decrease with PB pretreatment but did decrease in the liver slices. Enantiomeric ratios in the brain slices averaged 1.11 +/- 0.02 and were 0.76 +/- 0.03 in liver slices for the PB pretreated rats. These data indicate that the enantioselective metabolism of alpha-HCH by the brain is not the mechanism responsible for high ERs in this tissue.

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Preferential distribution of α-hexachlorocyclohexane into cerebral white matter

Cited by 16 publications

References 14 publications

A Stable Chemical SUMO1–Ubc9 Conjugate Specifically Binds as a Thioester Mimic to the RanBP2–E3 Ligase Complex

A Stable Chemical SUMO1–Ubc9 Conjugate Specifically Binds as a Thioester Mimic to the RanBP2–E3 Ligase Complex

Differential Toxicity and Environmental Fates of Hexachlorocyclohexane Isomers

Understanding Enantioselective Processes: A Laboratory Rat Model for α-Hexachlorocyclohexane Accumulation

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