A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research
Isatin (indole-2,3-dione) is an endogenous regulator, exhibiting a wide range of biological and pharmacological activities. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration. Good evidence exists that its effects are realized via interac...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-06-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/21/11/4187 |
id |
doaj-27189628fd6944bf8e985bf8a366ce2d |
---|---|
record_format |
Article |
spelling |
doaj-27189628fd6944bf8e985bf8a366ce2d2020-11-25T03:03:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-01214187418710.3390/ijms21114187A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further ResearchAlexei Medvedev0Arthur Kopylov1Olga Buneeva2Leonid Kurbatov3Olga Tikhonova4Alexis Ivanov5Victor Zgoda6Department of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, RussiaDepartment of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, RussiaDepartment of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, RussiaDepartment of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, RussiaDepartment of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, RussiaDepartment of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, RussiaDepartment of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, RussiaIsatin (indole-2,3-dione) is an endogenous regulator, exhibiting a wide range of biological and pharmacological activities. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration. Good evidence exists that its effects are realized via interaction with numerous isatin-binding proteins identified in the brain and peripheral tissues studied. In this study, we investigated the effect of a single dose administration of isatin to mice (100 mg/kg, 24 h) on differentially expressed proteins and a profile of the isatin-binding proteins in brain hemispheres. Isatin administration to mice caused downregulation of 31 proteins. However, these changes cannot be attributed to altered expression of corresponding genes. Although at this time point isatin influenced the expression of more than 850 genes in brain hemispheres (including 433 upregulated and 418 downregulated genes), none of them could account for the changes in the differentially expressed proteins. Comparative proteomic analysis of brain isatin-binding proteins of control and isatin-treated mice revealed representative groups of proteins sensitive to isatin administration. Control-specific proteins (n = 55) represent specific targets that interact directly with isatin. Appearance of brain isatin-binding proteins specific to isatin-treated mice (n = 94) may be attributed to the formation of new clusters of protein–protein interactions and/or novel binding sites induced by a high concentration of this regulator (ligand-induced binding sites). Thus, isatin administration produces multiple effects in the brain, which include changes in gene expression and also profiles of isatin-binding proteins and their interactomes. Further studies are needed for deeper insight into the mechanisms of the multilevel changes in the brain proteome induced by isatin. In the context of the neuroprotective action, these changes may be aimed at interruption of pathological links that begin to form after initiation of pathological processes.https://www.mdpi.com/1422-0067/21/11/4187Neuroprotector isatinmolecular targetsdifferentially expressed proteinsproteome analysisisatin-binding proteinsinteractome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexei Medvedev Arthur Kopylov Olga Buneeva Leonid Kurbatov Olga Tikhonova Alexis Ivanov Victor Zgoda |
spellingShingle |
Alexei Medvedev Arthur Kopylov Olga Buneeva Leonid Kurbatov Olga Tikhonova Alexis Ivanov Victor Zgoda A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research International Journal of Molecular Sciences Neuroprotector isatin molecular targets differentially expressed proteins proteome analysis isatin-binding proteins interactome |
author_facet |
Alexei Medvedev Arthur Kopylov Olga Buneeva Leonid Kurbatov Olga Tikhonova Alexis Ivanov Victor Zgoda |
author_sort |
Alexei Medvedev |
title |
A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research |
title_short |
A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research |
title_full |
A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research |
title_fullStr |
A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research |
title_full_unstemmed |
A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research |
title_sort |
neuroprotective dose of isatin causes multilevel changes involving the brain proteome: prospects for further research |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-06-01 |
description |
Isatin (indole-2,3-dione) is an endogenous regulator, exhibiting a wide range of biological and pharmacological activities. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration. Good evidence exists that its effects are realized via interaction with numerous isatin-binding proteins identified in the brain and peripheral tissues studied. In this study, we investigated the effect of a single dose administration of isatin to mice (100 mg/kg, 24 h) on differentially expressed proteins and a profile of the isatin-binding proteins in brain hemispheres. Isatin administration to mice caused downregulation of 31 proteins. However, these changes cannot be attributed to altered expression of corresponding genes. Although at this time point isatin influenced the expression of more than 850 genes in brain hemispheres (including 433 upregulated and 418 downregulated genes), none of them could account for the changes in the differentially expressed proteins. Comparative proteomic analysis of brain isatin-binding proteins of control and isatin-treated mice revealed representative groups of proteins sensitive to isatin administration. Control-specific proteins (n = 55) represent specific targets that interact directly with isatin. Appearance of brain isatin-binding proteins specific to isatin-treated mice (n = 94) may be attributed to the formation of new clusters of protein–protein interactions and/or novel binding sites induced by a high concentration of this regulator (ligand-induced binding sites). Thus, isatin administration produces multiple effects in the brain, which include changes in gene expression and also profiles of isatin-binding proteins and their interactomes. Further studies are needed for deeper insight into the mechanisms of the multilevel changes in the brain proteome induced by isatin. In the context of the neuroprotective action, these changes may be aimed at interruption of pathological links that begin to form after initiation of pathological processes. |
topic |
Neuroprotector isatin molecular targets differentially expressed proteins proteome analysis isatin-binding proteins interactome |
url |
https://www.mdpi.com/1422-0067/21/11/4187 |
work_keys_str_mv |
AT alexeimedvedev aneuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT arthurkopylov aneuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT olgabuneeva aneuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT leonidkurbatov aneuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT olgatikhonova aneuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT alexisivanov aneuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT victorzgoda aneuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT alexeimedvedev neuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT arthurkopylov neuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT olgabuneeva neuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT leonidkurbatov neuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT olgatikhonova neuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT alexisivanov neuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch AT victorzgoda neuroprotectivedoseofisatincausesmultilevelchangesinvolvingthebrainproteomeprospectsforfurtherresearch |
_version_ |
1724685261457063936 |