Peripherin Pathology

McLean, Jesse R.; Robertson, Janice

doi:10.1007/978-1-4419-6787-9_9

Cited by 2 publications

(3 citation statements)

References 164 publications

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“…Experiments with rat microsomes discovered three di-OHcongeners with PCB 3 (4-chlorobiphenyl), most likely because of the lack of phase 2 metabolism. 72 In the present study with living cells other di-OH-PCB 11 metabolites were below the detection limit because they are either minor metabolites or are rapidly converted to sulfated (Class 2.2), glucuronidated (Class 2.3) and methoxylated (Classes 3 and 4) metabolites. Also, it can be expected that similar to other lower chlorinated PCB congeners, PCB 11 catechols can be further oxidized to reactive and potential highly toxic PCB 11 quinones.…”

Section: Class 2 -Dihydroxylated Pcb 11 Metabolites and Their Conjugatescontrasting

confidence: 48%

“…Also, it can be expected that similar to other lower chlorinated PCB congeners, PCB 11 catechols can be further oxidized to reactive and potential highly toxic PCB 11 quinones. 35,40,[72][73][74][75][76] The presence of a di-OH-PCB 11 and the corresponding conjugated (Class 2.2 and 2.3) metabolites was confirmed after deconjugation, followed by derivatization and gas chromatographic analysis (Figs. S5-S7).…”

Section: Class 2 -Dihydroxylated Pcb 11 Metabolites and Their Conjugatesmentioning

confidence: 99%

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3,3′-Dichlorobiphenyl Is Metabolized to a Complex Mixture of Oxidative Metabolites, Including Novel Methoxylated Metabolites, by HepG2 Cells

Zhang

Flor

Ruíz

et al. 2020

Environ. Sci. Technol.

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3,3'-Dichlorobiphenyl (PCB 11) is a byproduct of industrial processes and detected in environmental samples. PCB 11 and its metabolites are present in human serum, and emerging evidence demonstrates that PCB 11 is a developmental neurotoxicant. However, little is known about the metabolism of PCB 11 in humans. Here we investigated the metabolism of PCB 11 and the associated metabolomics changes in HepG2 cells using untargeted high-resolution mass spectrometry. HepG2 cells were exposed for 24 h to PCB 11 in DMSO or DMSO alone. Cell culture media were analyzed with ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. Thirty different metabolites were formed by HepG2 cells exposed to 10 μM PCB 11, including monohydroxylated, dihydroxylated, hydroxylatedmethoxylated, and methoxylated-di-hydroxylated metabolites, and the corresponding sulfo and glucuronide conjugates. The methoxylated PCB metabolites were observed for the first time in a human-relevant model. 4-OH-PCB 11 (3,3'-dichlorobiphenyl-4-ol) and the corresponding catechol metabolite, 4,5-di-OH-PCB 11 (3',5-dichloro-3,4-dihydroxybiphenyl), were unambiguously

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Section: Class 2 -Dihydroxylated Pcb 11 Metabolites and Their Conjugatescontrasting

confidence: 48%

Section: Class 2 -Dihydroxylated Pcb 11 Metabolites and Their Conjugatesmentioning

confidence: 99%

3,3′-Dichlorobiphenyl Is Metabolized to a Complex Mixture of Oxidative Metabolites, Including Novel Methoxylated Metabolites, by HepG2 Cells

Zhang

Flor

Ruíz

et al. 2020

Environ. Sci. Technol.

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“…Following its discovery as a 57kDa Triton-insoluble protein (Portier et al, 1982; Tatemoto et al, 1982; Portier et al, 1983b; Portier et al, 1983a), peripherin was established as a type III IF protein based on its structural properties and ability to assemble into filaments by itself or together with either neurofilament proteins or vimentin (Portier et al, 1983a; Parysek and Goldman, 1987; Leonard et al, 1988; Thompson and Ziff, 1989; Cui et al, 1995; Ho et al, 1995; Athlan and Mushynski, 1997). Although its neuronal specificity and abundance in axons led early investigators to suspect that peripherin, like α-internexin, may be a subunit of neurofilaments (Portier et al, 1983a), little evidence has been brought to bear on this possibility (Barry et al, 2007; Mclean and Robertson, 2011). Moreover, other studies have supported the view that peripherin forms a separate filament system (Ferri et al, 1990; Troy et al, 1990; Wong and Oblinger, 1990; Beaulieu et al, 1999) although the evidence is indirect.…”

Section: Introductionmentioning

confidence: 99%

Peripherin Is a Subunit of Peripheral Nerve Neurofilaments: Implications for Differential Vulnerability of CNS and Peripheral Nervous System Axons

Yuan¹,

Sasaki²,

Kumar³

et al. 2012

Journal of Neuroscience

106

100

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Peripherin, a neuronal intermediate filament protein implicated in neurodegenerative disease, coexists with the neurofilament triplet proteins (NFL, NFM, and NFH) but has an unknown function. The earlier peak expression of peripherin than the triplet during brain development and its ability to form homopolymers, unlike the triplet, which are obligate heteropolymers, have supported a widely held view that peripherin and neurofilament triplet form separate filament systems. Here, we demonstrate, however, that despite a postnatal decline in expression, peripherin is as abundant as the triplet in the adult PNS and exists in a relatively fixed stoichiometry with these subunits. Peripherin exhibits a distribution pattern identical to those of triplet proteins in sciatic axons and co-localizes with NFL on single neurofilament by immunogold electron microscopy. Peripherin also co-assembles into a single network of filaments containing NFL, NFM, NFH with and without α-internexin in quadruple- or quintuple-transfected SW13 vim (−) cells. Genetically deleting NFL in mice dramatically reduces peripherin content in sciatic axons. Moreover, peripherin mutations has been shown to disrupt the neurofilament network in transfected SW13 vim(−) cells. These data show that peripherin and the neurofilament proteins are functionally interdependent. The results strongly support the view that rather than forming an independent structure, peripherin is a subunit of neurofilaments in the adult PNS. Our findings provide a basis for its close relationship with neurofilaments in PNS diseases associated with neurofilament accumulation.

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Peripherin Pathology

Cited by 2 publications

References 164 publications

3,3′-Dichlorobiphenyl Is Metabolized to a Complex Mixture of Oxidative Metabolites, Including Novel Methoxylated Metabolites, by HepG2 Cells

3,3′-Dichlorobiphenyl Is Metabolized to a Complex Mixture of Oxidative Metabolites, Including Novel Methoxylated Metabolites, by HepG2 Cells

Peripherin Is a Subunit of Peripheral Nerve Neurofilaments: Implications for Differential Vulnerability of CNS and Peripheral Nervous System Axons

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