Abstract:
:We previously reported a novel toxic peptide identified from the anthozoan Protopalythoa variabilis transcriptome which is homologous to a novel structural type of sodium channel toxin isolated from a parental species (Palythoa caribaeorum). The peptide was named, according to its homologous, as Pp V-shape α-helical peptide (PpVα) in the present study. Through molecular docking and dynamics simulation, linear and hairpin folded PpVα peptides were shown to be potential voltage-gated sodium channel blockers. Nowadays, sodium channel blockers have been the mainstream of the pharmacological management of epileptic seizures. Also, sodium channel blockers could promote neuronal survival by reducing sodium influx and reducing the likelihood of calcium importation resulting in suppressing microglial activation and protecting dopaminergic neurons from degeneration. The folded PpVα peptide could decrease pentylenetetrazol (PTZ)-induced c-fos and npas4a expression level leading to reverse PTZ-induced locomotor hyperactivity in zebrafish model. In vitro, the folded PpVα peptide protected PC12 cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity via activating heme oxygenase-1 (HO-1) and attenuating inducible nitric oxide synthase (iNOS) expression. In vivo, PpVα peptide suppressed the 6-OHDA-induced neurotoxicity on the locomotive behavior of zebrafish and, importantly, prevented the 6-OHDA-induced excessive ROS generation and subsequent dopaminergic neurons loss. This study indicates that the single S-S bond folded PpVα peptide arises as a new structural template to develop sodium channel blockers and provides an insight on the peptide discovery from cnidarian transcriptome to potentially manage epilepsy and neurodegenerative disorders.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Liao Q,Li S,Siu SWI,Morlighem JRL,Wong CTT,Wang X,Rádis-Baptista G,Lee SMdoi
10.1007/s00204-018-2334-5subject
Has Abstractpub_date
2019-01-01 00:00:00pages
189-206issue
1eissn
0340-5761issn
1432-0738pii
10.1007/s00204-018-2334-5journal_volume
93pub_type
杂志文章abstract::Labilization of lysosomal enzymes is often associated with the general process of inflammation. The present study investigated the effect of the pneumotoxin cadmium on the release and activity of two lung lysosomal enzymes. Incubation of rat lung lysosomes with cadmium resulted in the release of beta-glucuronidase but...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050181
更新日期:1995-01-01 00:00:00
abstract::In female rats dosed orally with 14C-hexachlorobenzene the extent of intestinal absorption of carbon-14 has been found to be dependent on the form of application. When the substance was given as a solution in oil about 80% of the dose administered was absorbed, but when given as an aqueous suspension only 6%. In anima...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00353283
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abstract::Primary hepatocytes are a widely used cell model to analyse the expression and regulation of hepatic cytochrome P450 (CYP) isoenzymes. Transforming growth factor-beta1 (TGF-beta1) was previously shown to inhibit constitutive and induced CYP1 expression in human cell lines and primary hepatocytes but not in rat cells. ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050667
更新日期:2000-05-01 00:00:00
abstract::In order to clarify the possible mechanism of hepatocarcinogenesis induced by piperonyl butoxide, we attempted to identify the transcription factor activated by piperonyl butoxide in the male ICR mouse liver. Administration of 0.6% piperonyl butoxide for 24 h elevated the level of liver nuclear proteins that bind to a...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-008-0283-0
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abstract::Nine bispyridinium oximes containing two pyridinium rings linked by dimethylether were synthesised. Each compound had on one of the pyridinium rings a hydroxyiminomethyl group in position 2 or 4, while the other ring was unsubstituted or had a methyl or a hydroxyiminomethyl group in position 2 or 4. The reactivating p...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00296900
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abstract::The effect of culture medium on glutathione (GSH) dependent detoxification defence system of primary cultured hepatocyte from either male or female rats was studied. Intracellular reduced (GSH) and oxidized glutathione (GSSG), and six GSH-related enzyme activities, including GSH peroxidase (GSH Px), GSH reductase (GSH...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050345
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abstract::Particle-induced carcinogenicity is not well understood, but might involve inflammation. The proinflammatory cytokine tumor necrosis factor (TNF) is considered to be an important mediator in inflammation. We investigated its role in particle-induced inflammation and DNA damage in mice with and without TNF signaling. T...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-004-0613-9
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abstract::Boric acid and sodium borates are currently classified as being toxic to reproduction under "Category 1B" with the hazard statement of "H360 FD" in the European CLP regulation. This has prompted studies on boron-mediated reprotoxic effects in male workers in boron mining areas and boric acid production plants. By cont...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-018-2238-4
更新日期:2018-08-01 00:00:00
abstract::Cadmium chloride was administered by gavage to female rats 5 days a week for 5 weeks, then during mating and gestation periods at doses of 0.04, 0.4, and 4 mg Cd/kg/day. Treatment with cadmium neither affected the survival and fertility of females, nor produced overt fetotoxic effects. Fetal cadmium concentration was ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01234482
更新日期:1983-12-01 00:00:00
abstract::Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsH...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-018-2194-z
更新日期:2018-05-01 00:00:00
abstract::The effects of cadmium exposure during pregnancy (by means of daily subcutaneous injections of 4.4 mumol/kg to the mother) on the neonates were investigated. No effect was observed on fetal or neonatal body weights, nor on neonatal liver weights. These parameters were examined up to 5 weeks after birth. The weight of ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00334632
更新日期:1989-01-01 00:00:00
abstract::The current management of rodent pest populations is based on second-generation anticoagulant rodenticides (SGAR). These molecules, of which difethialone is part, are much more efficient than the first generation. Nevertheless, this efficiency comes with a major drawback, SGARs are tissue persistent that increases the...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-020-02662-0
更新日期:2020-03-01 00:00:00
abstract::Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the org...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02547-x
更新日期:2019-10-01 00:00:00
abstract::When rats were dosed with 14 microgram/kg 3H-isoproterenol, 3H-radioactivity was measurable in the liver until 48 h. This amount was not different in livers of animals which have been pretreated with diethyl maleate. After exhaustive extraction, a significant amount of 3H-radioactivity from isoproterenol could be dete...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00343273
更新日期:1977-12-30 00:00:00
abstract::The peroxisome proliferator class of non-genotoxic rodent hepatocarcinogens cause hepatocyte DNA synthesis, peroxisome proliferation and liver tumours when administered to rats and mice, but fail to induce S-phase or peroxisome proliferation in hepatocytes from other species including guinea-pigs, dogs, and primates i...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050483
更新日期:1998-02-01 00:00:00
abstract::Unsaturated compounds are known to cause false-positive reactions in the local lymph node assay (LLNA) but not in the guinea pig maximization test. We have tested a panel of substances (succinic acid, undecylenic acid, 1-octyn-3-ol, fumaric acid, maleic acid, linoleic acid, oleic acid, alpha-linolenic acid, squalene, ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-015-1527-4
更新日期:2016-04-01 00:00:00
abstract::A new class of potent anticancer drugs, alkylphosphocholines has been recognized lately. Miltefosine (Hexadecylphosphochlorine, HPC) has been found to express select antineoplastic effect on human breast cancer skin metastases with simultaneous preservation of bone marrow proliferative activity and low clastogenicity....
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-005-0010-z
更新日期:2006-01-01 00:00:00
abstract::The aim of this study was to assess the neurotoxicity of diazinon oxon (DZO), a major in vivo metabolite of the phosphorothionate insecticide diazinon (DZ), on differentiating mouse N2a neuroblastoma cells. When used at concentrations of 1, 5 and 10 microM, DZO did not cause cell death but it impaired the outgrowth of...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-008-0339-1
更新日期:2009-04-01 00:00:00
abstract::Aliphatic nitriles are a class of chemicals used in high volumes in the production of plastics and elastomers, in organic synthesis, and in production of a number of food packaging containers. Toxicity and metabolism of acrylonitrile (AN) are well characterized. On the other hand, minimal information is available on t...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF03208340
更新日期:1994-01-01 00:00:00
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journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040100213
更新日期:2001-04-01 00:00:00
abstract::A study was conducted to determine the levels of cis-diamminedichloroplatinum (II) (cisplatin) in plasma proteins and hemoglobin of cancer patients after cisplatin chemotherapy. Thirty-seven cancer patients with different type of cancers (lung, esophageal, urinary tract, and testicular cancer, melanoma, osteosarcoma e...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00303124
更新日期:1989-01-01 00:00:00
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journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040000116
更新日期:2000-07-01 00:00:00
abstract::The development and application of high throughput in vitro assays is an important development for risk assessment in the twenty-first century. However, there are still significant challenges to incorporate in vitro assays into routine toxicity testing practices. In this paper, a robust learning approach was developed...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-018-2260-6
更新日期:2018-09-01 00:00:00
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journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-014-1319-2
更新日期:2015-08-01 00:00:00
abstract::The EU-EuroMix project adopted the strategy of the European Food Safety Authority (EFSA) for cumulative risk assessment, which limits the number of chemicals to consider in a mixture to those that induce a specific toxicological phenotype. These so-called cumulative assessment groups (CAGs) are refined at several leve...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-018-2320-y
更新日期:2018-12-01 00:00:00
abstract::Previous histomorphometric studies led us to hypothesize that suppression of hepatocellular regeneration and the repair of the hepatolobular architecture was involved besides bioactivation phenomenon in the progressive and irreversible phase of toxicity resulting from CD + CCl4 interaction. We have recently observed s...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00303125
更新日期:1989-01-01 00:00:00
abstract::Polyclonal antibodies raised toward a debrisoquine 4-hydroxylating cytochrome P-450 species purified from rat liver (P-450UT-A) were used to determine which monooxygenase reactions are linked to debrisoquine hydroxylation in human liver. Anti P-450UT-A did not inhibit the oxidation of dimethylnitrosamine, morphine, di...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00296955
更新日期:1987-01-01 00:00:00
abstract::Although polybrominated naphthalenes (PBNs) are contaminants of the commercial fire retardant fireMaster BP-6, the individual PBN isomers have not been identified. In order to study PBNs possessing an analogous level of bromination to those found in fireMaster BP-6, three synthetic PBN mixtures, averaging 5.0, 5.3, an...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00346051
更新日期:1984-07-01 00:00:00
abstract::The mycotoxins altertoxin I and II (ATX I and II) are secondary metabolites produced by Alternaria alternata fungi and may occur as food and feed contaminants, especially after long storage periods. Although the toxic potential of altertoxins has been previously investigated, little is known about the pathways that pl...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-016-1726-7
更新日期:2017-01-01 00:00:00
abstract::The nephrotoxicity of 4-amino-3-S-glutathionylphenol (PAP-GSH), a known metabolite of 4-amino-phenol (PAP), was determined in male Fischer 344 rats. Administration of a single dose of 40 or 60 mumol kg-1 caused a marked elevation in blood urea nitrogen and an increase in the urinary excretion of glucose, protein and g...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF03035706
更新日期:1994-01-01 00:00:00