Toxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae

PcActx peptide, identified from the transcriptome of zoantharian Palythoa caribaeorum, was clustered into the phylogeny of analgesic polypeptides from sea anemone Heteractis crispa (known as APHC peptides). APHC peptides were considered as inhibitors of transient receptor potential cation channel su...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiufen Wang, Qiwen Liao, Hanbin Chen, Guiyi Gong, Shirley Weng In Siu, Qian Chen, Hiotong Kam, Carolina Oi Lam Ung, Kwok-Kuen Cheung, Gandhi Rádis-Baptista, Clarence Tsun Ting Wong, Simon Ming-Yuen Lee
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	zoantharian PcActx peptide transcriptomics analysis TRPV1 channel anti-epilepsy zebrafish Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d7319914ec294906b2ff256da5e334e6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d7319914ec294906b2ff256da5e334e6
record_format	dspace
spelling	oai:doaj.org-article:d7319914ec294906b2ff256da5e334e62021-12-02T01:05:07ZToxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae1663-981210.3389/fphar.2021.763089https://doaj.org/article/d7319914ec294906b2ff256da5e334e62021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.763089/fullhttps://doaj.org/toc/1663-9812PcActx peptide, identified from the transcriptome of zoantharian Palythoa caribaeorum, was clustered into the phylogeny of analgesic polypeptides from sea anemone Heteractis crispa (known as APHC peptides). APHC peptides were considered as inhibitors of transient receptor potential cation channel subfamily V member 1 (TRPV1). TRPV1 is a calcium-permeable channel expressed in epileptic brain areas, serving as a potential target for preventing epileptic seizures. Through in silico and in vitro analysis, PcActx peptide was shown to be a potential TRPV1 channel blocker. In vivo studies showed that the linear and oxidized PcActx peptides caused concentration-dependent increases in mortality of zebrafish larvae. However, monotreatment with PcActx peptides below the maximum tolerated doses (MTD) did not affect locomotor behavior. Moreover, PcActx peptides (both linear and oxidized forms) could effectively reverse pentylenetetrazol (PTZ)-induced seizure-related behavior in zebrafish larvae and prevent overexpression of c-fos and npas4a at the mRNA level. The excessive production of ROS induced by PTZ was markedly attenuated by both linear and oxidized PcActx peptides. It was also verified that the oxidized PcActx peptide was more effective than the linear one. In particular, oxidized PcActx peptide notably modulated the mRNA expression of genes involved in calcium signaling and γ-aminobutyric acid (GABA)ergic-glutamatergic signaling, including calb1, calb2, gabra1, grm1, gria1b, grin2b, gat1, slc1a2b, gad1b, and glsa. Taken together, PcActx peptide, as a novel neuroactive peptide, exhibits prominent anti-epileptic activity, probably through modulating calcium signaling and GABAergic-glutamatergic signaling, and is a promising candidate for epilepsy management.Xiufen WangQiwen LiaoQiwen LiaoHanbin ChenGuiyi GongShirley Weng In SiuQian ChenHiotong KamCarolina Oi Lam UngKwok-Kuen CheungGandhi Rádis-BaptistaClarence Tsun Ting WongSimon Ming-Yuen LeeFrontiers Media S.A.articlezoantharianPcActx peptidetranscriptomics analysisTRPV1 channelanti-epilepsyzebrafishTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	zoantharian PcActx peptide transcriptomics analysis TRPV1 channel anti-epilepsy zebrafish Therapeutics. Pharmacology RM1-950
spellingShingle	zoantharian PcActx peptide transcriptomics analysis TRPV1 channel anti-epilepsy zebrafish Therapeutics. Pharmacology RM1-950 Xiufen Wang Qiwen Liao Qiwen Liao Hanbin Chen Guiyi Gong Shirley Weng In Siu Qian Chen Hiotong Kam Carolina Oi Lam Ung Kwok-Kuen Cheung Gandhi Rádis-Baptista Clarence Tsun Ting Wong Simon Ming-Yuen Lee Toxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae
description	PcActx peptide, identified from the transcriptome of zoantharian Palythoa caribaeorum, was clustered into the phylogeny of analgesic polypeptides from sea anemone Heteractis crispa (known as APHC peptides). APHC peptides were considered as inhibitors of transient receptor potential cation channel subfamily V member 1 (TRPV1). TRPV1 is a calcium-permeable channel expressed in epileptic brain areas, serving as a potential target for preventing epileptic seizures. Through in silico and in vitro analysis, PcActx peptide was shown to be a potential TRPV1 channel blocker. In vivo studies showed that the linear and oxidized PcActx peptides caused concentration-dependent increases in mortality of zebrafish larvae. However, monotreatment with PcActx peptides below the maximum tolerated doses (MTD) did not affect locomotor behavior. Moreover, PcActx peptides (both linear and oxidized forms) could effectively reverse pentylenetetrazol (PTZ)-induced seizure-related behavior in zebrafish larvae and prevent overexpression of c-fos and npas4a at the mRNA level. The excessive production of ROS induced by PTZ was markedly attenuated by both linear and oxidized PcActx peptides. It was also verified that the oxidized PcActx peptide was more effective than the linear one. In particular, oxidized PcActx peptide notably modulated the mRNA expression of genes involved in calcium signaling and γ-aminobutyric acid (GABA)ergic-glutamatergic signaling, including calb1, calb2, gabra1, grm1, gria1b, grin2b, gat1, slc1a2b, gad1b, and glsa. Taken together, PcActx peptide, as a novel neuroactive peptide, exhibits prominent anti-epileptic activity, probably through modulating calcium signaling and GABAergic-glutamatergic signaling, and is a promising candidate for epilepsy management.
format	article
author	Xiufen Wang Qiwen Liao Qiwen Liao Hanbin Chen Guiyi Gong Shirley Weng In Siu Qian Chen Hiotong Kam Carolina Oi Lam Ung Kwok-Kuen Cheung Gandhi Rádis-Baptista Clarence Tsun Ting Wong Simon Ming-Yuen Lee
author_facet	Xiufen Wang Qiwen Liao Qiwen Liao Hanbin Chen Guiyi Gong Shirley Weng In Siu Qian Chen Hiotong Kam Carolina Oi Lam Ung Kwok-Kuen Cheung Gandhi Rádis-Baptista Clarence Tsun Ting Wong Simon Ming-Yuen Lee
author_sort	Xiufen Wang
title	Toxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae
title_short	Toxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae
title_full	Toxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae
title_fullStr	Toxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae
title_full_unstemmed	Toxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae
title_sort	toxic peptide from palythoa caribaeorum acting on the trpv1 channel prevents pentylenetetrazol-induced epilepsy in zebrafish larvae
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d7319914ec294906b2ff256da5e334e6
work_keys_str_mv	AT xiufenwang toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT qiwenliao toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT qiwenliao toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT hanbinchen toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT guiyigong toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT shirleywenginsiu toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT qianchen toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT hiotongkam toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT carolinaoilamung toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT kwokkuencheung toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT gandhiradisbaptista toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT clarencetsuntingwong toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae AT simonmingyuenlee toxicpeptidefrompalythoacaribaeorumactingonthetrpv1channelpreventspentylenetetrazolinducedepilepsyinzebrafishlarvae
_version_	1718403347387514880

Toxic Peptide From Palythoa caribaeorum Acting on the TRPV1 Channel Prevents Pentylenetetrazol-Induced Epilepsy in Zebrafish Larvae

Ejemplares similares