Cargando…
c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury
In this article, we review the literature regarding the role of c-Jun N-terminal kinases (JNKs) in cerebral and myocardial ischemia/reperfusion injury. Numerous studies demonstrate that JNK-mediated signaling pathways play an essential role in cerebral and myocardial ischemia/reperfusion injury. JNK...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041399/ https://www.ncbi.nlm.nih.gov/pubmed/30026697 http://dx.doi.org/10.3389/fphar.2018.00715 |
_version_ | 1783338987546476544 |
---|---|
author | Shvedova, Maria Anfinogenova, Yana Atochina-Vasserman, Elena N. Schepetkin, Igor A. Atochin, Dmitriy N. |
author_facet | Shvedova, Maria Anfinogenova, Yana Atochina-Vasserman, Elena N. Schepetkin, Igor A. Atochin, Dmitriy N. |
author_sort | Shvedova, Maria |
collection | PubMed |
description | In this article, we review the literature regarding the role of c-Jun N-terminal kinases (JNKs) in cerebral and myocardial ischemia/reperfusion injury. Numerous studies demonstrate that JNK-mediated signaling pathways play an essential role in cerebral and myocardial ischemia/reperfusion injury. JNK-associated mechanisms are involved in preconditioning and post-conditioning of the heart and the brain. The literature and our own studies suggest that JNK inhibitors may exert cardioprotective and neuroprotective properties. The effects of modulating the JNK-depending pathways in the brain and the heart are reviewed. Cardioprotective and neuroprotective mechanisms of JNK inhibitors are discussed in detail including synthetic small molecule inhibitors (AS601245, SP600125, IQ-1S, and SR-3306), ion channel inhibitor GsMTx4, JNK-interacting proteins, inhibitors of mixed-lineage kinase (MLK) and MLK-interacting proteins, inhibitors of glutamate receptors, nitric oxide (NO) donors, and anesthetics. The role of JNKs in ischemia/reperfusion injury of the heart in diabetes mellitus is discussed in the context of comorbidities. According to reviewed literature, JNKs represent promising therapeutic targets for protection of the brain and the heart against ischemic stroke and myocardial infarction, respectively. However, different members of the JNK family exert diverse physiological properties which may not allow for systemic administration of non-specific JNK inhibitors for therapeutic purposes. Currently available candidate JNK inhibitors with high therapeutic potential are identified. The further search for selective JNK3 inhibitors remains an important task. |
format | Online Article Text |
id | pubmed-6041399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60413992018-07-19 c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury Shvedova, Maria Anfinogenova, Yana Atochina-Vasserman, Elena N. Schepetkin, Igor A. Atochin, Dmitriy N. Front Pharmacol Pharmacology In this article, we review the literature regarding the role of c-Jun N-terminal kinases (JNKs) in cerebral and myocardial ischemia/reperfusion injury. Numerous studies demonstrate that JNK-mediated signaling pathways play an essential role in cerebral and myocardial ischemia/reperfusion injury. JNK-associated mechanisms are involved in preconditioning and post-conditioning of the heart and the brain. The literature and our own studies suggest that JNK inhibitors may exert cardioprotective and neuroprotective properties. The effects of modulating the JNK-depending pathways in the brain and the heart are reviewed. Cardioprotective and neuroprotective mechanisms of JNK inhibitors are discussed in detail including synthetic small molecule inhibitors (AS601245, SP600125, IQ-1S, and SR-3306), ion channel inhibitor GsMTx4, JNK-interacting proteins, inhibitors of mixed-lineage kinase (MLK) and MLK-interacting proteins, inhibitors of glutamate receptors, nitric oxide (NO) donors, and anesthetics. The role of JNKs in ischemia/reperfusion injury of the heart in diabetes mellitus is discussed in the context of comorbidities. According to reviewed literature, JNKs represent promising therapeutic targets for protection of the brain and the heart against ischemic stroke and myocardial infarction, respectively. However, different members of the JNK family exert diverse physiological properties which may not allow for systemic administration of non-specific JNK inhibitors for therapeutic purposes. Currently available candidate JNK inhibitors with high therapeutic potential are identified. The further search for selective JNK3 inhibitors remains an important task. Frontiers Media S.A. 2018-07-05 /pmc/articles/PMC6041399/ /pubmed/30026697 http://dx.doi.org/10.3389/fphar.2018.00715 Text en Copyright © 2018 Shvedova, Anfinogenova, Atochina-Vasserman, Schepetkin and Atochin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Shvedova, Maria Anfinogenova, Yana Atochina-Vasserman, Elena N. Schepetkin, Igor A. Atochin, Dmitriy N. c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury |
title | c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury |
title_full | c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury |
title_fullStr | c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury |
title_full_unstemmed | c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury |
title_short | c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury |
title_sort | c-jun n-terminal kinases (jnks) in myocardial and cerebral ischemia/reperfusion injury |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041399/ https://www.ncbi.nlm.nih.gov/pubmed/30026697 http://dx.doi.org/10.3389/fphar.2018.00715 |
work_keys_str_mv | AT shvedovamaria cjunnterminalkinasesjnksinmyocardialandcerebralischemiareperfusioninjury AT anfinogenovayana cjunnterminalkinasesjnksinmyocardialandcerebralischemiareperfusioninjury AT atochinavassermanelenan cjunnterminalkinasesjnksinmyocardialandcerebralischemiareperfusioninjury AT schepetkinigora cjunnterminalkinasesjnksinmyocardialandcerebralischemiareperfusioninjury AT atochindmitriyn cjunnterminalkinasesjnksinmyocardialandcerebralischemiareperfusioninjury |