TY - JOUR
T1 - Anti-epileptic Kunitz-like peptides discovered in the branching coral Acropora digitifera through transcriptomic analysis
AU - Chen, Hanbin
AU - Siu, Shirley Weng In
AU - Wong, Clarence Tsun Ting
AU - Qiu, Jianwen
AU - Cheung, Alex Kwok Kuen
AU - Lee, Simon Ming Yuen
N1 - Funding Information:
This work was supported by University of Macau was funded by the Science and Technology Development Fund, Macau SAR (File no. FDCT0058/2019/A1 and 0016/2019/AKP), University of Macau (Ref No: MYRG2020-00183-ICMS, MYRG2022-00263-ICMS and CPG2022-00023-ICMS) and Shenzhen-Hong Kong-Macao Science and Technology Innovation Project (Category C) (Ref No: EF038/ICMS-LMY/2021/SZSTIC), Shenzhen Science and Technology Innovation Committee. The Hong Kong Polytechnic University (Project ID. P0006304). The Environmental and Conservation Fund of Hong Kong (Grant no. 34/2019), and Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong laboratory (Guangzhou) (Grant nos. GMl2019ZD0404, SMSEGl20SC02). This work was performed in part at the high performance computing cluster (HPCC) which is supported by information and communication technology office (ICTO) of the University of Macau.
Funding Information:
This work was supported by University of Macau was funded by the Science and Technology Development Fund, Macau SAR (File no. FDCT0058/2019/A1 and 0016/2019/AKP), University of Macau (Ref No: MYRG2020-00183-ICMS, MYRG2022-00263-ICMS and CPG2022-00023-ICMS) and Shenzhen-Hong Kong-Macao Science and Technology Innovation Project (Category C) (Ref No: EF038/ICMS-LMY/2021/SZSTIC), Shenzhen Science and Technology Innovation Committee. The Hong Kong Polytechnic University (Project ID. P0006304). The Environmental and Conservation Fund of Hong Kong (Grant no. 34/2019), and Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong laboratory (Guangzhou) (Grant nos. GMl2019ZD0404, SMSEGl20SC02). This work was performed in part at the high performance computing cluster (HPCC) which is supported by information and communication technology office (ICTO) of the University of Macau.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/9
Y1 - 2022/9
N2 - Approximately 50 million people are suffering from epilepsy worldwide. Corals have been used for treating epilepsy in traditional Chinese medicine, but the mechanism of this treatment is unknown. In this study, we analyzed the transcriptome of the branching coral Acropora digitifera and obtained its Kyoto Encyclopedia of Genes and Genomes (KEGG), EuKaryotic Orthologous Groups (KOG) and Gene Ontology (GO) annotation. Combined with multiple sequence alignment and phylogenetic analysis, we discovered three polypeptides, we named them AdKuz1, AdKuz2 and AdKuz3, from A. digitifera that showed a close relationship to Kunitz-type peptides. Molecular docking and molecular dynamics simulation indicated that AdKuz1 to 3 could interact with GABAA receptor but AdKuz2–GABAA remained more stable than others. The biological experiments showed that AdKuz1 and AdKuz2 exhibited an anti-inflammatory effect by decreasing the aberrant level of nitric oxide (NO), IL-6, TNF-α and IL-1β induced by LPS in BV-2 cells. In addition, the pentylenetetrazol (PTZ)-induced epileptic effect on zebrafish was remarkably suppressed by AdKuz1 and AdKuz2. AdKuz2 particularly showed superior anti-epileptic effects compared to the other two peptides. Furthermore, AdKuz2 significantly decreased the expression of c-fos and npas4a, which were up-regulated by PTZ treatment. In addition, AdKuz2 reduced the synthesis of glutamate and enhanced the biosynthesis of gamma-aminobutyric acid (GABA). In conclusion, the results indicated that AdKuz2 may affect the synthesis of glutamate and GABA and enhance the activity of the GABAA receptor to inhibit the symptoms of epilepsy. We believe, AdKuz2 could be a promising anti-epileptic agent and its mechanism of action should be further investigated.
AB - Approximately 50 million people are suffering from epilepsy worldwide. Corals have been used for treating epilepsy in traditional Chinese medicine, but the mechanism of this treatment is unknown. In this study, we analyzed the transcriptome of the branching coral Acropora digitifera and obtained its Kyoto Encyclopedia of Genes and Genomes (KEGG), EuKaryotic Orthologous Groups (KOG) and Gene Ontology (GO) annotation. Combined with multiple sequence alignment and phylogenetic analysis, we discovered three polypeptides, we named them AdKuz1, AdKuz2 and AdKuz3, from A. digitifera that showed a close relationship to Kunitz-type peptides. Molecular docking and molecular dynamics simulation indicated that AdKuz1 to 3 could interact with GABAA receptor but AdKuz2–GABAA remained more stable than others. The biological experiments showed that AdKuz1 and AdKuz2 exhibited an anti-inflammatory effect by decreasing the aberrant level of nitric oxide (NO), IL-6, TNF-α and IL-1β induced by LPS in BV-2 cells. In addition, the pentylenetetrazol (PTZ)-induced epileptic effect on zebrafish was remarkably suppressed by AdKuz1 and AdKuz2. AdKuz2 particularly showed superior anti-epileptic effects compared to the other two peptides. Furthermore, AdKuz2 significantly decreased the expression of c-fos and npas4a, which were up-regulated by PTZ treatment. In addition, AdKuz2 reduced the synthesis of glutamate and enhanced the biosynthesis of gamma-aminobutyric acid (GABA). In conclusion, the results indicated that AdKuz2 may affect the synthesis of glutamate and GABA and enhance the activity of the GABAA receptor to inhibit the symptoms of epilepsy. We believe, AdKuz2 could be a promising anti-epileptic agent and its mechanism of action should be further investigated.
KW - Anti-epileptic
KW - GABA
KW - Kunitz peptide
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85130696338&partnerID=8YFLogxK
U2 - 10.1007/s00204-022-03311-4
DO - 10.1007/s00204-022-03311-4
M3 - Journal article
AN - SCOPUS:85130696338
SN - 0340-5761
VL - 96
SP - 2589
EP - 2608
JO - Archives of Toxicology
JF - Archives of Toxicology
IS - 9
ER -