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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.912757/full |
| _version_ | 1811248457009070080 |
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| author | Madhu Nath Patrice Elie Fort Patrice Elie Fort |
| author_facet | Madhu Nath Patrice Elie Fort Patrice Elie Fort |
| author_sort | Madhu Nath |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T15:28:25Z |
| format | Article |
| id | doaj.art-be21b97ae4d2474089e497477626b125 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-12T15:28:25Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-be21b97ae4d2474089e497477626b1252022-12-22T03:27:11ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-05-011610.3389/fnins.2022.912757912757αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase BMadhu Nath0Patrice Elie Fort1Patrice Elie Fort2Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, United StatesDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, United StatesDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United StatesPhosphatidylinositol 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.https://www.frontiersin.org/articles/10.3389/fnins.2022.912757/fullαA-crystallinprotein kinase Bretinal neuronsapoptosisneuroprotection |
| spellingShingle | Madhu Nath Patrice Elie Fort Patrice Elie Fort αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B Frontiers in Neuroscience αA-crystallin protein kinase B retinal neurons apoptosis neuroprotection |
| 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 | αA-crystallin protein kinase B retinal neurons apoptosis neuroprotection |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.912757/full |
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