Inhibiting the interaction between apoptosis-inducing factor and cyclophilin A prevents brain injury in neonatal mice after hypoxia-ischemia.

Administration, Intranasal Animals Animals, Newborn Apoptosis / drug effects Apoptosis Inducing Factor / antagonists & inhibitors CA1 Region, Hippocampal / drug effects Caspases / physiology Cell Death / drug effects Cyclophilins / antagonists & inhibitors Female Gray Matter / pathology Hypoxia-Ischemia, Brain / pathology Male Mice Mice, Inbred C57BL Neuroprotective Agents / pharmacology Organelle Biogenesis Sex Characteristics White Matter / pathology
Apoptosis-inducing factor Blocking peptide Brain injury Cyclophilin A Hypoxia-ischemia Immature brain

Journal

Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217

Informations de publication

Date de publication:
07 2020
Historique:
received: 01 10 2019
revised: 07 03 2020
accepted: 02 04 2020
pubmed: 12 4 2020
medline: 29 6 2021
entrez: 12 4 2020
Statut: ppublish

Résumé

The interaction between apoptosis-inducing factor (AIF) and cyclophilin A (CypA) has been shown to contribute to caspase-independent apoptosis. Blocking the AIF/CypA interaction protects against glutamate-induced neuronal cell death in vitro, and the purpose of this study was to determine the in vivo effect of an AIF/CypA interaction blocking peptide (AIF(370-394)-TAT) on neonatal mouse brain injury after hypoxia-ischemia (HI). The pups were treated with AIF (370-394)-TAT peptide intranasally prior to HI. Brain injury was significantly reduced at 72 h after HI in the AIF(370-394)-TAT peptide treatment group compared to vehicle-only treatment for both the gray matter and the subcortical white matter, and the neuroprotection was more pronounced in males than in females. Neuronal cell death was evaluated in males at 8 h and 24 h post-HI, and it was decreased significantly in the CA1 region of the hippocampus and the nucleus habenularis region after AIF(370-394)-TAT treatment. Caspase-independent apoptosis was decreased in the cortex, striatum, and nucleus habenularis after AIF(370-394)-TAT treatment, but no significant change was found on caspase-dependent apoptosis as indicated by the number of active caspase-3-labeled cells. Further analysis showed that both AIF and CypA nuclear accumulation were decreased after treatment with the AIF(370-394)-TAT peptide. These results suggest that AIF(370-394)-TAT inhibited AIF/CypA translocation to the nucleus and reduced HI-induced caspase-independent apoptosis and brain injury in young male mice, suggesting that blocking AIF/CypA might be a potential therapeutic target for neonatal brain injury.

Identifiants

DOI: 10.1016/j.neuropharm.2020.108088 PMID: 32277944
pubmed: 32277944
pii: S0028-3908(20)30156-8
doi: 10.1016/j.neuropharm.2020.108088
pii:
doi:

Substances chimiques

Apoptosis Inducing Factor 0
Neuroprotective Agents 0
Caspases EC 3.4.22.-
Cyclophilins EC 5.2.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108088

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Auteurs

Juan Rodriguez (J)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden.

Cuicui Xie (C)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden.

Tao Li (T)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Department of Pediatrics, Children's Hospital of Zhengzhou University, Zhengzhou, China.

Yanyan Sun (Y)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Department of Anatomy, School of Basic Medical Science, Zhengzhou University, Zhengzhou, 450001, China.

Yafeng Wang (Y)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Department of Pediatrics, Children's Hospital of Zhengzhou University, Zhengzhou, China.

Yiran Xu (Y)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Kenan Li (K)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Shan Zhang (S)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Kai Zhou (K)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Yong Wang (Y)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Carina Mallard (C)

Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Centre of Perinatal Medicine and Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden.

Henrik Hagberg (H)

Centre of Perinatal Medicine and Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Dept of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.

Nunzianna Doti (N)

Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, Napoli, 80134, Italy.

Xiaoyang Wang (X)

Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Centre of Perinatal Medicine and Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden.

Changlian Zhu (C)

Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Centre of Perinatal Medicine and Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: changlian.zhu@neuro.gu.se.

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Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par voie topique › Administration par voie muqueuse › Administration par voie nasale › Inhibiting the interaction between...
questionsmedicales.fr › Eucaryotes › Animaux › Inhibiting the interaction between...
questionsmedicales.fr › Eucaryotes › Animaux › Groupes animaux › Animaux nouveau-nés › Inhibiting the interaction between...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Inhibiting the interaction between...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines liant le poly-adp-ribose › Facteur inducteur d'apoptose › Inhibiting the interaction between...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Hippocampe › Région CA1 de l'hippocampe › Inhibiting the interaction between...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines régulatrices de l'apoptose › Caspases › Inhibiting the interaction between...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Inhibiting the interaction between...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs des médicaments › Immunophilines › Cyclophilines › Inhibiting the interaction between...
questionsmedicales.fr › Système nerveux › Système nerveux central › Moelle spinale › Substance grise › Inhibiting the interaction between...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Signes et symptômes respiratoires › Hypoxie › Hypoxie cérébrale › Hypoxie-ischémie du cerveau › Inhibiting the interaction between...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Inhibiting the interaction between...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Inhibiting the interaction between...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Neuroprotecteurs › Inhibiting the interaction between...
questionsmedicales.fr › Phénomènes biologiques › Biogenèse des organelles › Inhibiting the interaction between...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Caractères sexuels › Inhibiting the interaction between...
questionsmedicales.fr › Système nerveux › Système nerveux central › Moelle spinale › Substance blanche › Inhibiting the interaction between...