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αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B

Phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway mediates pro-survival function in neurons. In the retina, PI3K/AKT/mTOR signaling pathway is related to the early pathogenesis of diabetic retinopathy. Signaling molecules in the membrane-initiated signaling pathway exhibiting neuroprotective f...

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Autores principales: Nath, Madhu, Fort, Patrice Elie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163390/
https://www.ncbi.nlm.nih.gov/pubmed/35669493
http://dx.doi.org/10.3389/fnins.2022.912757
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author Nath, Madhu
Fort, Patrice Elie
author_facet Nath, Madhu
Fort, Patrice Elie
author_sort Nath, Madhu
collection PubMed
description Phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway mediates pro-survival function in neurons. In the retina, PI3K/AKT/mTOR signaling pathway is related to the early pathogenesis of diabetic retinopathy. Signaling molecules in the membrane-initiated signaling pathway exhibiting neuroprotective function interacts with the PI3K/Akt pathway as an important survival pathway. Molecular chaperone α-crystallins are known to potentially interact and/or regulate various pro-survival and pro-apoptotic proteins to regulate cell survival. Among these demonstrated mechanisms, they are well-reported to regulate and inhibit apoptosis by interacting and sequestrating the proapoptotic proteins such as Bax and Bcl-Xs. We studied the importance of metabolic stress-induced enhanced Akt signaling and αA-crystallin interdependence for exhibiting neuroprotection in metabolically challenged retinal neurons. For the first time, this study has revealed that αA-crystallin and activated Akt are significantly neuroprotective in the stressed retinal neurons, independent of each other. Furthermore, the study also highlighted that significant inhibition of the PI3K-Akt pathway does not alter the neuroprotective ability of αA-crystallin in stressed retinal neurons. Interestingly, our study also demonstrated that in the absence of Akt activation, αA-crystallin inhibits the translocation of Bax in the mitochondria during metabolic stress, and this function is regulated by the phosphorylation of αA-crystallin on residue 148.
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spelling pubmed-91633902022-06-05 αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B Nath, Madhu Fort, Patrice Elie Front Neurosci Neuroscience Phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway mediates pro-survival function in neurons. In the retina, PI3K/AKT/mTOR signaling pathway is related to the early pathogenesis of diabetic retinopathy. Signaling molecules in the membrane-initiated signaling pathway exhibiting neuroprotective function interacts with the PI3K/Akt pathway as an important survival pathway. Molecular chaperone α-crystallins are known to potentially interact and/or regulate various pro-survival and pro-apoptotic proteins to regulate cell survival. Among these demonstrated mechanisms, they are well-reported to regulate and inhibit apoptosis by interacting and sequestrating the proapoptotic proteins such as Bax and Bcl-Xs. We studied the importance of metabolic stress-induced enhanced Akt signaling and αA-crystallin interdependence for exhibiting neuroprotection in metabolically challenged retinal neurons. For the first time, this study has revealed that αA-crystallin and activated Akt are significantly neuroprotective in the stressed retinal neurons, independent of each other. Furthermore, the study also highlighted that significant inhibition of the PI3K-Akt pathway does not alter the neuroprotective ability of αA-crystallin in stressed retinal neurons. Interestingly, our study also demonstrated that in the absence of Akt activation, αA-crystallin inhibits the translocation of Bax in the mitochondria during metabolic stress, and this function is regulated by the phosphorylation of αA-crystallin on residue 148. Frontiers Media S.A. 2022-05-20 /pmc/articles/PMC9163390/ /pubmed/35669493 http://dx.doi.org/10.3389/fnins.2022.912757 Text en Copyright © 2022 Nath and Fort. https://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 Neuroscience
Nath, Madhu
Fort, Patrice Elie
αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B
title αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B
title_full αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B
title_fullStr αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B
title_full_unstemmed αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B
title_short αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B
title_sort αa-crystallin mediated neuroprotection in the retinal neurons is independent of protein kinase b
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163390/
https://www.ncbi.nlm.nih.gov/pubmed/35669493
http://dx.doi.org/10.3389/fnins.2022.912757
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