UM
Novel neurotoxic peptides from Protopalythoa variabilis virtually interact with voltage-gated sodium channel and display anti-epilepsy and neuroprotective activities in zebrafish
Liao Q.1; Li S.1; Siu S.W.I.1; Morlighem J.-E.R.L.2; Wong C.T.T.3; Wang X.1; Radis-Baptista G.2; Lee S.M.-Y.1
2019-01-21
Source PublicationArchives of Toxicology
ISSN14320738 03405761
Volume93Issue:1Pages:189-206
AbstractWe 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.
KeywordAnti-epilepsy Disulfide bond Neuroactive peptides Neuroprotection Protein docking Voltage-gated sodium ion channel blocker
DOI10.1007/s00204-018-2334-5
URLView the original
Language英語
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Universidade de Macau
2.Universidade Federal do Ceara
3.Chinese University of Hong Kong
Recommended Citation
GB/T 7714
Liao Q.,Li S.,Siu S.W.I.,et al. Novel neurotoxic peptides from Protopalythoa variabilis virtually interact with voltage-gated sodium channel and display anti-epilepsy and neuroprotective activities in zebrafish[J]. Archives of Toxicology,2019,93(1):189-206.
APA Liao Q..,Li S..,Siu S.W.I..,Morlighem J.-E.R.L..,Wong C.T.T..,...&Lee S.M.-Y..(2019).Novel neurotoxic peptides from Protopalythoa variabilis virtually interact with voltage-gated sodium channel and display anti-epilepsy and neuroprotective activities in zebrafish.Archives of Toxicology,93(1),189-206.
MLA Liao Q.,et al."Novel neurotoxic peptides from Protopalythoa variabilis virtually interact with voltage-gated sodium channel and display anti-epilepsy and neuroprotective activities in zebrafish".Archives of Toxicology 93.1(2019):189-206.
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