Cargando…
Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis
Ketamine is a dissociative anesthetic and a non-competitive NMDAR antagonist. At subanesthetic dose, ketamine can relieve pain and work as a fast-acting antidepressant, but the underlying molecular mechanism remains elusive. This study aimed to investigate the mode of action underlying the effects o...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389495/ https://www.ncbi.nlm.nih.gov/pubmed/34437591 http://dx.doi.org/10.1371/journal.pone.0256390 |
_version_ | 1783742871819517952 |
---|---|
author | Choi, Yunjung Kim, Baeksun Ham, Suji Chung, Sooyoung Maeng, Sungho Kim, Hye-Sun Im, Heh-In |
author_facet | Choi, Yunjung Kim, Baeksun Ham, Suji Chung, Sooyoung Maeng, Sungho Kim, Hye-Sun Im, Heh-In |
author_sort | Choi, Yunjung |
collection | PubMed |
description | Ketamine is a dissociative anesthetic and a non-competitive NMDAR antagonist. At subanesthetic dose, ketamine can relieve pain and work as a fast-acting antidepressant, but the underlying molecular mechanism remains elusive. This study aimed to investigate the mode of action underlying the effects of acute subanesthetic ketamine treatment by bioinformatics analyses of miRNAs in the medial prefrontal cortex of male C57BL/6J mice. Gene Ontology and KEGG pathway analyses of the genes putatively targeted by ketamine-responsive prefrontal miRNAs revealed that acute subanesthetic ketamine modifies ubiquitin-mediated proteolysis. Validation analysis suggested that miR-148a-3p and miR-128-3p are the main players responsible for the subanesthetic ketamine-mediated alteration of ubiquitin-mediated proteolysis through varied regulation of ubiquitin ligases E2 and E3. Collectively, our data imply that the prefrontal miRNA-dependent modulation of ubiquitin-mediated proteolysis is at least partially involved in the mode of action by acute subanesthetic ketamine treatment. |
format | Online Article Text |
id | pubmed-8389495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83894952021-08-27 Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis Choi, Yunjung Kim, Baeksun Ham, Suji Chung, Sooyoung Maeng, Sungho Kim, Hye-Sun Im, Heh-In PLoS One Research Article Ketamine is a dissociative anesthetic and a non-competitive NMDAR antagonist. At subanesthetic dose, ketamine can relieve pain and work as a fast-acting antidepressant, but the underlying molecular mechanism remains elusive. This study aimed to investigate the mode of action underlying the effects of acute subanesthetic ketamine treatment by bioinformatics analyses of miRNAs in the medial prefrontal cortex of male C57BL/6J mice. Gene Ontology and KEGG pathway analyses of the genes putatively targeted by ketamine-responsive prefrontal miRNAs revealed that acute subanesthetic ketamine modifies ubiquitin-mediated proteolysis. Validation analysis suggested that miR-148a-3p and miR-128-3p are the main players responsible for the subanesthetic ketamine-mediated alteration of ubiquitin-mediated proteolysis through varied regulation of ubiquitin ligases E2 and E3. Collectively, our data imply that the prefrontal miRNA-dependent modulation of ubiquitin-mediated proteolysis is at least partially involved in the mode of action by acute subanesthetic ketamine treatment. Public Library of Science 2021-08-26 /pmc/articles/PMC8389495/ /pubmed/34437591 http://dx.doi.org/10.1371/journal.pone.0256390 Text en © 2021 Choi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Choi, Yunjung Kim, Baeksun Ham, Suji Chung, Sooyoung Maeng, Sungho Kim, Hye-Sun Im, Heh-In Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis |
title | Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis |
title_full | Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis |
title_fullStr | Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis |
title_full_unstemmed | Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis |
title_short | Subanesthetic ketamine rapidly alters medial prefrontal miRNAs involved in ubiquitin-mediated proteolysis |
title_sort | subanesthetic ketamine rapidly alters medial prefrontal mirnas involved in ubiquitin-mediated proteolysis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389495/ https://www.ncbi.nlm.nih.gov/pubmed/34437591 http://dx.doi.org/10.1371/journal.pone.0256390 |
work_keys_str_mv | AT choiyunjung subanestheticketaminerapidlyaltersmedialprefrontalmirnasinvolvedinubiquitinmediatedproteolysis AT kimbaeksun subanestheticketaminerapidlyaltersmedialprefrontalmirnasinvolvedinubiquitinmediatedproteolysis AT hamsuji subanestheticketaminerapidlyaltersmedialprefrontalmirnasinvolvedinubiquitinmediatedproteolysis AT chungsooyoung subanestheticketaminerapidlyaltersmedialprefrontalmirnasinvolvedinubiquitinmediatedproteolysis AT maengsungho subanestheticketaminerapidlyaltersmedialprefrontalmirnasinvolvedinubiquitinmediatedproteolysis AT kimhyesun subanestheticketaminerapidlyaltersmedialprefrontalmirnasinvolvedinubiquitinmediatedproteolysis AT imhehin subanestheticketaminerapidlyaltersmedialprefrontalmirnasinvolvedinubiquitinmediatedproteolysis |